Background
p-Hydroxyphenylglycine (DL-p-Hydroxyphenylglycine, DL-p-HPG for English abbreviation) with a chemical name of DL-p-hydroxy-alpha-aminophenylacetic acid is mainly used for producing antibiotics such as amoxicillin and cefadroxil. At present, the synthesis method mainly adopts a method of taking glyoxylic acid, phenol and sulfamic acid as raw materials in industry, and the mechanism of the three-molecule reaction is generally considered to be that phenol and glyoxylic acid firstly react to generate a p-hydroxymandelic acid intermediate, and then react with sulfamic acid to generate DL-p-HPG.
Early US patent US5336805(1994-08-09) disclosed in detail the synthesis of DL-p-HPG in aqueous solution with molar yield of DL-p-HPG up to 65% based on glyoxylic acid as the main starting material. The molar yield of p-hydroxyphenylglycine synthesis in industrial production is usually 55-60%, the technical economy of production is seriously affected due to low yield in industrial production, and the environmental protection treatment cost is very high due to a large amount of generated phenol pollutants.
The main reason that the synthesis yield of DL-p-HPG is not high is that the selectivity of the reaction of phenol and glyoxylic acid on hydroxymandelic acid is usually 70-76%, and ortho-hydroxymandelic acid and phenolic polymer impurities with complex structures are simultaneously generated in the reaction. The yield of the subsequent ammoniation step of hydroxymandelic acid is usually 80% to 85%. In the industrial production process of p-hydroxy-phenyl-hydantoin, p-hydroxy-phenyl-acetic acid, vanillin and piperonal, the problem of low reaction yield of the phenolic compound and glyoxylic acid also exists. For example, chinese patent CN101811947B (2014-02-26) discloses that in an alkaline aqueous solution, the use of a copper or iron salt can reduce the ortho-position product of the reaction of a phenolic compound with glyoxylic acid, and correspondingly increase the selectivity of the para-position product by 3% to 4%. Chinese patent CN105910834A (2016-08-31) discloses that a complex of metal copper or iron is used as a catalyst, and a phenolic compound and glyoxylic acid can also undergo an addition reaction in the absence of a solvent and without the addition of an acid-base catalyst, with a selectivity of 75%.
Chinese patent CN109759043B (2021-08-13) discloses that the synthesis yield of DL-p-HPG can be greatly improved by adopting a small amount of silicon-aluminum oxide solid acid catalyst, but the reproducibility of the experimental result is poor. Chinese patent CN107987023A (2018-05-04) discloses a preparation method for synthesizing p-hydroxy-phenyl-hydantoin by solid acid catalysis, which adopts ZrO2/SiO2The effect of improving the synthesis yield is not obvious enough by the supported solid sulfuric acid catalyst. Since the surface of the solid acid catalyst is saturated and adsorbed by water molecules in an aqueous solution, it is difficult to exhibit a good catalytic effect.
Chinese patent CN1103300460A (2019-10-15) discloses that in an organic solvent, the selectivity of p-hydroxy-phenyl-hydantoin is obviously improved under the catalysis of various types of solid acid, but p-hydroxy-phenyl-hydantoin products are not dissolved in an acidic aqueous solution and a common organic solvent, and the products cannot be separated from the solid acid catalyst, so that the application is difficult. The solid acid catalyst has small corrosivity and no special requirements on the material of production equipment, and particularly, the solid phosphoric acid catalyst has a plurality of successful application cases in chemical production, and stimulates professionals to search continuously.
Solid acids are substances that donate protons or accept electrons according to the definition of Broensted and Lewis acids and bases. The substance capable of donating a proton is called a Broensted acid (B acid or protonic acid for short) and the substance capable of accepting an electron pair is called a Lewis acid (L acid for short). Solid Phosphoric Acid Catalysts (SPAC) belong to the group of protonic acid catalysts. The acid sites of the solid phosphoric acid catalyst are mainly derived from the phosphoric acid adsorbed on the catalyst. Phosphoric acid existing on the carrier in different forms comprises orthophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid and polyphosphoric acid, the phosphoric acid in different forms has different proton-donating ability, the proton-donating ability of the pyrophosphoric acid is obviously stronger than that of the orthophosphoric acid, and the proton-donating ability of the polyphosphoric acid is stronger than that of the pyrophosphoric acid.
The composition and performance of the solid phosphoric acid catalyst depends to a large extent on the support and the preparation method. The carrier of the solid phosphoric acid catalyst is also a solid acid catalyst, and is generally divided into two main categories of natural aluminosilicate and artificially synthesized inorganic oxide. The natural aluminosilicate is mainly diatomite, bentonite, montmorillonite, kaolin and activated clay, and the impurities of the natural aluminosilicate can be removed by acid treatment, so that the specific surface area and the thermal stability of the natural aluminosilicate are improved. The synthetic inorganic oxide mainly contains SiO2、Al2O3、WO3、TiO2And ZrO2And the combination thereof, diatomite or silica gel is generally selected as a carrier of the solid phosphoric acid catalyst in industry.
The preparation method of the solid phosphoric acid catalyst mainly comprises an impregnation method and a blending method. The impregnation method generally uses diatomite as a carrier and orthophosphoric acid as an impregnation solution, and the solid is separated, dried and roasted to obtain the solid phosphoric acid catalyst. The blending method is that diatomite and polyphosphoric acid are used as raw materials, boric acid or other additives are added, drying, roasting and activating are carried out after uniform mixing, and the obtained solid phosphoric acid catalyst has high activity and crushing strength and low production cost. Researches find that the solid phosphoric acid formed at the temperature of 300-350 ℃ has a loose porous structure, has hydrolyzability, high acid content and good activity; the solid phosphoric acid formed at 400-700 ℃ has chemical stability and hydrolysis resistance.
Disclosure of Invention
The invention aims to provide a method for catalytically synthesizing p-hydroxyphenylglycine by solid phosphoric acid, which is characterized in that solid phosphoric acid loaded by fly ash floating beads is used as a catalyst, the solid phosphoric acid catalyst and a fly ash floating bead cocatalyst play a synergistic role, the formation of phenolic polymer impurities is inhibited through the immobilization of reaction raw materials, the preparation yield of DL-p-HPG is improved, the method comprises five parts, namely solid phosphoric acid catalyst preparation, DL-p-HPG sulfate preparation, solid phosphoric acid catalyst separation circulation, alkane solvent recovery circulation and DL-p-HPG preparation, and the specific steps are as follows:
step 1, uniformly mixing phosphoric acid and fly ash floating beads, and controlling P contained in the phosphoric acid2O5The mass ratio of the fly ash floating beads to the fly ash floating beads is 0.05-0.3: 1; heating at the temperature of 120-170 ℃ to enable the phosphoric acid and the fly ash floating bead to react and convert into a solid mixture, then roasting at the temperature of 400-700 ℃ for 0.5-2h, cooling in air and crushing to 20-40 meshes to obtain the fly ash floating bead loaded solid phosphoric acid catalyst, wherein the specific surface area of the solid phosphoric acid catalyst is 3-10m2Acid strength Ho = -8.7 to-5.8; the phosphoric acid is one of orthophosphoric acid, pyrophosphoric acid, polyphosphoric acid or a mixture thereof, and P contained in the phosphoric acid2O5The mass fraction of (A) is 40-80%; the fly ash floating bead comprises the following components in percentage by mass: SiO 22 50%-65%,Al2O3 25%-35%,Fe2O3 4 to 9 percent of the total weight of the powder, 2.5 to 15 percent of alkali metal and alkaline earth metal oxide, 20 to 40 meshes of granularity and 0.3 to 0.4m of specific surface area2Per g, specific gravity of 0.25-0.45g/cm3;
Step 2, respectively adding phenol, sulfamic acid and a solid phosphoric acid catalyst into the alkane solvent, and controlling the feeding mass ratio of the phenol, the sulfamic acid, the solid phosphoric acid catalyst and the alkane solvent to be 1: 1-1.2: 1.5-4: 5-15; heating and refluxing at 70-100 ℃, adding 50% of glyoxylic acid aqueous solution by mass fraction into the reaction solution within 0.5-2h, simultaneously carrying out azeotropic distillation to separate water in the reactants, and controlling the feeding molar ratio of glyoxylic acid, phenol and sulfamic acid to be 1: 1.0-1.1: 1.0-1.2, keeping the temperature for 2-6h after the feeding is finished, and completely converting the glyoxylic acid in the reactants; the alkane solvent is one of n-hexane, cyclohexane, n-heptane or a mixture thereof;
step 3, adding deionized water into the reactant, controlling the molar ratio of the deionized water to the raw material glyoxylic acid to be 15-30:1, and heating and refluxing at 65-70 ℃ to dissolve the DL-p-HPG sulfate solid in the aqueous solution; filtering and separating the solid phosphoric acid catalyst, washing the product carried by the solid phosphoric acid catalyst by deionized water, and drying for recycling;
step 4, separating alkane solvent phase in the reaction solution, washing the product carried by the alkane solvent phase with deionized water, and recycling the product after distillation and recovery;
step 5, adding saturated ammonia water into the aqueous solution, and neutralizing the aqueous solution to pH = 3-5; then cooling to 15-20 ℃, separating out white precipitate, washing with deionized water, soaking and washing with methanol, and drying at 80-110 ℃ to obtain the DL-p-HPG product with the content of 99.5% and the molar yield of 75-80%.
The inventor is inspired from the successful case of the industrial application of the solid phosphoric acid, creatively expands the catalysis of the solid phosphoric acid to be applied to the preparation of DL-p-HPG, and designs and selects the fly ash floating bead which is cheap and easy to obtain as a carrier and a synthesis promoter of the solid phosphoric acid catalyst. The innovation is that the fly ash floating bead is a novel solid acid catalyst, and the specific surface area and the catalytic activity of the fly ash floating bead can be enlarged by using phosphoric acid for etching. Main component SiO of fly ash floating bead2、Al2O3And Fe2O3The formation of organic reaction intermediate product carbonium ions can be promoted in the catalytic reaction, and the performance of the solid phosphoric acid catalyst is enhanced. The fly ash floating bead has small specific gravity and can be uniformly dispersed in a reaction solvent. The fly ash floating beads have larger granularity, convenient separation and recovery and long service life.
The invention gives full play to the catalytic property of the iron oxide component in the fly ash floating bead, the iron oxide catalyst exists in the form of insoluble oxide, silicate and phosphate, can limit the concentration of free iron ions, can exert the catalytic action and can prevent phenol from oxidative discoloration. Different from the prior art that the natural aluminum silicate compound containing trace ferric oxide and the artificially synthesized oxide carrier containing no iron are adopted; and is completely different from the molecular sieve additionally added with the iron-containing component, and has substantive characteristics and remarkable progress.
The fly ash floating bead is a component of waste residue discharged from a coal-fired power plant, has a large chemical composition range, and has a large specific surface area and adsorption activity as well as a main component of SiO2、Al2O3And Fe2O3Is an oxide with good thermal stability formed after high-temperature combustion, is a good carrier of a solid phosphoric acid catalyst, and contains B,Trace elements such as Mo, Se, Sr, Ba, Mn, Ti, Zr and the like are also effective components of the solid phosphoric acid catalyst. The fly ash floating beads supplied in the market are various in variety so as to meet different purposes of building materials, wastewater treatment adsorbing materials, photocatalyst carriers and the like. The fly ash floating bead selected by the invention comprises the following components in percentage by mass: SiO 22 50%-65%,Al2O3 25%-35%,Fe2O3 4 to 9 percent of the total weight of the powder, 2.5 to 15 percent of alkali metal and alkaline earth metal oxide, 20 to 40 meshes of granularity and 0.3 to 0.4m of specific surface area2Per g, specific gravity of 0.25-0.45g/cm3. After acid and alkali immersion etching and other modes of activation, the specific surface area and the adsorption activity of the composite material can be increased by tens of times.
Orthophosphoric acid is 85% liquid at room temperature and contains P2O5In order to stir and mix the fly ash floating bead with 61.5 percent of orthophosphoric acid in a laboratory, the orthophosphoric acid can be diluted by adding water until the P is contained2O5The mass fraction of the solid phosphoric acid is 40 percent, then the mixture of the orthophosphoric acid and the fly ash floating beads is heated at the temperature of 120-170 ℃ to ensure that the orthophosphoric acid solution and the fly ash floating beads are reacted and converted into a solid mixture, and then the solid mixture is roasted at the temperature of 400-700 ℃ for 0.5-2h to obtain the insoluble solid phosphoric acid catalyst.
The pyrophosphate is a solid at room temperature and has a melting point of 54 ℃ and contains P2O5The mass fraction of (b) was 79.8%. The method of soaking the fly ash floating bead after dissolving in water is uneconomical, the fly ash floating bead and the water can be uniformly mixed in a stirrer in the form of solid powder, then the mixture is heated at the temperature of 120-700 ℃ to be reacted with the fly ash floating bead to be converted into a solid mixture, and then the solid mixture is roasted at the temperature of 400-700 ℃ for 0.5-2h to obtain the insoluble solid phosphoric acid catalyst.
Concentration of phosphoric acid, pyrophosphoric acid and polyphosphoric acid, P contained in the phosphoric acid, pyrophosphoric acid and polyphosphoric acid is customary in the industry2O5The mass fraction of (3) may be represented by the mass fraction of phosphoric acid contained therein. For example, 80% by weight of orthophosphoric acid containing P2O5The mass fraction of (A) is 57.9%; 100% by mass of pyrophosphoric acid containing P2O5The mass fraction of (b) was 79.8%.
According to the application experiment effect and principle analysis of the solid phosphoric acid catalyst, the catalyst has good catalytic activity on the addition reaction of phenol and glyoxylic acid to generate p-hydroxymandelic acid and the reaction of ammonification of the hydroxymandelic acid to generate p-hydroxyphenylglycine. The Solid Phosphoric Acid Catalyst (SPAC) can adsorb phenol in the immobilized solution, so that chemical reaction is carried out on the surface of the solid phosphoric acid catalyst, thereby changing the reaction activity of the phenol, accelerating the reaction speed and changing the ratio of forming various isomers.
The Solid Phosphoric Acid Catalyst (SPAC) can adsorb glyoxylic acid in an immobilized reaction solution, the glyoxylic acid is converted into carbonium ions with a glycollic acid structure on the surface of the solid phosphoric acid catalyst, active hydrogen on a phenol ring is then abstracted, the carbonium ions with the glycollic acid structure are connected to a para-position carbon atom of a phenolic hydroxyl group in a complex form to generate p-hydroxyphenylglycine, and the chemical reaction is shown as follows:
CHOCOOH + H+ SPAC-=HOC+HCOOH + SPAC-
HOHC+COOH + C6H5OH+ SPAC-=DL-p-HPG + H+ SPAC-
as the addition reaction of the glyoxylic acid and the phenol is carried out on the surface of the solid phosphoric acid catalyst, the carbonium ions of the glycollic acid structure are not completely separated from the complex constraint of the solid phosphoric acid catalyst, and the carbonium ions of the glycollic acid structure with large molecular volume are difficult to enter the ortho position of the phenolic hydroxyl group and are easier to enter the para position of the phenolic hydroxyl group to generate the p-hydroxyphenylglycine due to the influence of the steric hindrance effect, the selectivity of the DL-p-HPG synthesis reaction is improved.
The amination reaction of hydroxymandelic acid to p-hydroxyphenylglycine is also an acid-catalyzed reaction, since under alkaline conditions, the amination reaction is not very productive. In the presence of a solid phosphoric acid catalyst, sulfamic acid can be fed according to a reaction metering ratio without large excess feeding, so that the consumption of sulfamic acid raw materials is reduced. In experiments, orthophosphoric acid, pyrophosphoric acid, polyphosphoric acid or fly ash floating beads independently have an effect of improving the selectivity of DL-p-HPG preparation, but the orthophosphoric acid, pyrophosphoric acid, polyphosphoric acid or fly ash floating beads form a solid phosphoric acid catalyst after roasting treatment, so that the solid phosphoric acid catalyst not only can exert a synergistic effect, but also overcomes the defects of water solubility and corrosivity of phosphoric acid.
The solid phosphoric acid catalyst has the acid strength equivalent to that of sulfuric acid with the mass fraction of 60-80%, and is roasted at the high temperature of 400-700 ℃ to achieve the aims of insolubility in water, high mechanical strength and long cycle service life. The composition of the solid phosphoric acid catalyst is very complex and can be regarded as a solid solution of silica, alumina, iron oxide, phosphoric acid, pyrophosphoric acid, polyphosphoric acid, silicon phosphate, aluminum phosphate and iron phosphate.
Because the solid acid catalyst can play a good catalytic role under the anhydrous condition, the invention adopts an azeotropic distillation mode to separate the moisture brought by the raw material glyoxylic acid aqueous solution, and a large amount of moisture can decompose and inactivate the solid phosphoric acid catalyst. The reason why the use of anhydrous glyoxylic acid was not selected is that the presence of a small amount of moisture helped the immobilization of the glyoxylic acid and sulfamic acid starting materials on the surface of the solid phosphoric acid catalyst.
The invention adopts the synthesis of DL-p-HPG in alkane solvent which is chemically inert, cheap and easy to obtain, and particularly selects the alkane solvent which can be azeotropic with water and has proper boiling point and reaction temperature, such as n-hexane, cyclohexane or n-heptane. The solid phosphoric acid catalyst can chemically adsorb a small amount of water brought by the solid glyoxylic acid raw material, and the chemical reaction formula is as follows:
Si3(PO4)4 + 6H2O = 3SiO2 + 4H3PO4
2AlPO4+ 3H2O = Al2O3 + 2H3PO4
H4P2O7+ H2O = 2H3PO4
the two measures of azeotropic dehydration and chemisorption dehydration adopted in the invention ensure that the addition reaction of phenol and glyoxylic acid can be carried out under the condition of basically no water and a small amount of water.
In the invention, phenol, glyoxylic acid and sulfamic acid are not dissolved in alkane solvent, the alkane solvent is only used as an inert reactant dispersion medium and a heat transfer medium, the phenol and glyoxylic acid raw materials are melted into liquid when reaching the self melting point at the reaction temperature of 70-100 ℃, and then are adsorbed and immobilized on a solid phosphoric acid catalyst, the chemical reaction is carried out on the active point of the solid phosphoric acid catalyst, and DL-p-HPG sulfate generated by the reaction is also adsorbed on the solid phosphoric acid catalyst in a solid form.
In the invention, deionized water is added after the chemical reaction is finished, so that DL-p-HPG sulfate can be completely dissolved, and three immiscible phases of the solid phosphoric acid catalyst, the alkane solvent and the aqueous solution are formed. Filtering and separating the solid phosphoric acid catalyst, washing the product carried by the solid phosphoric acid catalyst by deionized water, and drying the solid phosphoric acid catalyst for recycling. In the invention, the fly ash floating beads with larger particle size are selected as the carrier, so that the separation and washing of the solid phosphoric acid catalyst can be industrially implemented.
In the invention, the alkane solvent and the aqueous solution form two mutually insoluble phases, the alkane solvent is separated, the aqueous solution carried by the alkane solvent is washed by deionized water, and the alkane solvent can be recycled after distillation dehydration and impurity separation.
The water solution of the invention contains DL-p-HPG sulfate and a small amount of soluble phenolic polymer impurities, and the insoluble polymer impurities are adsorbed or extracted by a solid phosphoric acid catalyst and an alkane solvent. The reaction aqueous solution was further neutralized with concentrated aqueous ammonia, and at pH =3-5, DL-p-HPG was released from the easily soluble sulfate, and a poorly soluble DL-p-HPG white precipitate was formed. If the pH value after ammonia neutralization is more than 5, the residual phenolic polymer impurities are separated out together to form a DL-p-HPG precipitate with pink color. If the phenol polymer impurities cannot be completely removed by washing with deionized water, the phenol polymer impurities can be removed by soaking and washing with methanol, and loose DL-p-HPG white powder is obtained after precipitation and drying.
The advantages and the beneficial effects of the invention are embodied in that:
(1) the fly ash floating beads are used as a carrier and a synthesis cocatalyst of the solid phosphoric acid catalyst, and the fly ash floating beads and the synthesis cocatalyst play a synergistic effect, so that the catalytic activity of the solid phosphoric acid catalyst is improved;
(2) the iron component in the solid phosphoric acid catalyst in the form of oxide, silicate and phosphate can play a role in catalysis and can prevent excessive free iron ions from oxidizing and discoloring phenol;
(3) the solid phosphoric acid catalyst surface phenol adsorption immobilization, glyoxylic acid adsorption complexation, inhibits the generation of phenolic polymers, and improves the selectivity of DL-p-HPG synthesis.
The method for measuring the acid strength of the sample by adopting the Hammett indicator color-changing method comprises the following specific steps: accurately weighing 0.1 g of sample subjected to drying pretreatment, placing the sample into a small test tube, adding 2mL of cyclohexane, adding 1 drop of indicator, shaking, observing the change of the surface color of the sample, and determining the acid strength of the sample.
In the invention, a precipitation method is adopted for semi-quantitative detection of residual glyoxylic acid in reaction liquid, 1mL of reaction liquid is taken and added into 50mL of dilute hydrochloric acid saturated solution of 2, 4-dinitrophenylhydrazine, and if yellow precipitate of the 2, 4-dinitrophenylhydrazone is not generated, the added glyoxylic acid raw material is considered to be completely converted.
In the invention, the content of DL-p-HPG is measured by an HPLC method, and a chromatographic column is C18 (5 mu m, 250mm multiplied by 4.6 mm); the mobile phase is CH3CN∶H2O∶H3PO410: 90: 0.01 (volume ratio); the flow rate is 1 mL/min; the detection wavelength was 210 nm.
In the invention, the main raw material glyoxylic acid is a commercially available glyoxylic acid aqueous solution with the mass fraction of 50%, and sulfamic acid, phenol, orthophosphoric acid, pyrophosphoric acid, n-hexane, cyclohexane, n-heptane and ammonia water are commercially available chemical reagents.
The fly ash floating bead is a commercial fly ash floating bead for a power plant, and comprises the following components in percentage by mass: SiO 22 50%-65%,Al2O3 25%-35%,Fe2O3 4 to 9 percent of the total weight of the powder, 2.5 to 15 percent of alkali metal and alkaline earth metal oxide, 20 to 40 meshes of granularity and 0.3 to 0.4m of specific surface area2Per g, specific gravity of 0.25-0.45g/cm3。