Using hydroxypropyl methylcellulose (HPMC) as raw material, acetic anhydride and propionic anhydride as esterification agents, the esterification reaction in pyridine prepared hydroxypropyl methylcellulose acetate and hydroxypropyl methylcellulose Cellulose propionate. By changing the amount of solvent used in the system, a product with better properties and substitution degree was obtained. The substitution degree was determined by titration method, and the product was characterized and tested for performance. The results showed that the reaction system was reacted at 110°C for 1-2.5 h, and deionized water was used as the precipitating agent after the reaction, and powdery products with a degree of substitution greater than 1 (theoretical degree of substitution was 2) could be obtained. It has good solubility in various organic solvents such as ethyl ester, acetone, acetone/water, etc.
Key words: hydroxypropyl methylcellulose; hydroxypropyl methylcellulose acetate; hydroxypropyl methylcellulose propionate
Hydroxypropylmethylcellulose (HPMC) is a non-ionic polymer compound and a cellulose ether with a wide range of uses. As an excellent chemical additive, HPMC is often used in various fields and is called “industrial monosodium glutamate”. Hydroxypropyl methylcellulose (HPMC) not only has good emulsifying, thickening, and binding functions, but also can be used to maintain moisture and protect colloids. It is widely used in many fields such as food, medicine, coatings, textiles, and agriculture. . Modification of hydroxypropyl methylcellulose can change some of its properties, so that it can be better used in a certain field. The molecular formula of its monomer is C10H18O6.
In recent years, research on hydroxypropyl methylcellulose derivatives has gradually become a hot spot. By modifying hydroxypropyl methylcellulose, various derivative compounds with different properties can be obtained. For example, the introduction of acetyl groups can change the flexibility of medical coating films.
The modification of hydroxypropyl methylcellulose is usually carried out in the presence of an acid catalyst such as concentrated sulfuric acid. The experiment usually uses acetic acid as a solvent. The reaction conditions are cumbersome and time-consuming, and the resulting product has a low degree of substitution. (less than 1).
In this paper, acetic anhydride and propionic anhydride were used as esterification agents to modify hydroxypropyl methylcellulose to prepare hydroxypropyl methylcellulose acetate and hydroxypropyl methylcellulose propionate. By exploring conditions such as solvent selection (pyridine), solvent dosage, etc., it is hoped that a product with better properties and substitution degree can be obtained through a relatively simple method. In this paper, through experimental research, the target product with a powdery precipitate and a degree of substitution greater than 1 was obtained, which provided some theoretical guidance for the production of hydroxypropyl methylcellulose acetate and hydroxypropyl methylcellulose propionate.
1. Experimental part
1.1 Materials and reagents
Pharmaceutical grade hydroxypropyl methylcellulose (KIMA CHEMICAL CO.,LTD, 60HD100, methoxyl mass fraction 28%-30%, hydroxypropoxyl mass fraction 7%-12%); acetic anhydride, AR, Sinopharm Group Chemical Reagent Co., Ltd.; Propionic Anhydride, AR, West Asia Reagent; Pyridine, AR, Tianjin Kemiou Chemical Reagent Co., Ltd.; methanol, ethanol, ether, ethyl acetate, acetone, NaOH and HCl are commercially available analytically pure.
KDM thermostat electric heating mantle, JJ-1A speed measuring digital display electric stirrer, NEXUS 670 Fourier transform infrared spectrometer.
1.2 Preparation of hydroxypropyl methylcellulose acetate
A certain amount of pyridine was added into the three-neck flask, and then 2.5 g of hydroxypropyl methylcellulose was added thereto, the reactants were stirred evenly, and the temperature was raised to 110°C. Add 4 mL of acetic anhydride, react at 110 °C for 1 h, stop heating, cool to room temperature, add a large amount of deionized water to precipitate the product, filter with suction, wash with deionized water for several times until the eluate is neutral, and dry the product save.
1.3 Preparation of hydroxypropyl methylcellulose propionate
A certain amount of pyridine was added into the three-necked flask, and then 0.5 g of hydroxypropyl methylcellulose was added thereto, the reactants were stirred evenly, and the temperature was raised to 110°C. Add 1.1 mL of propionic anhydride, react at 110 °C for 2.5 h, stop heating, cool to room temperature, add a large amount of deionized water to precipitate the product, filter with suction, wash with deionized water for several times until the eluate is medium property, store the product dry.
1.4 Determination of infrared spectroscopy
The hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate, hydroxypropyl methylcellulose propionate and KBr were mixed and ground respectively, and then pressed into tablets to determine the infrared spectrum.
1.5 Determination of degree of substitution
Prepare NaOH and HCl solutions with a concentration of 0.5 mol/L, and carry out calibration to determine the exact concentration; weigh 0.5 g of hydroxypropylmethylcellulose acetate (hydroxypropylmethylcellulose propionic acid ester) in a 250 mL Erlenmeyer flask, add 25 mL of acetone and 3 drops of phenolphthalein indicator, mix well, then add 25 mL of NaOH solution, stir and saponify on an electromagnetic stirrer for 2 h; titrate with HCI until the red color of the solution disappears, record The volume V1 (V2) of hydrochloric acid consumed; use the same method to measure the volume V0 of hydrochloric acid consumed by hydroxypropyl methylcellulose, and calculate the degree of substitution.
1.6 Solubility experiment
Take an appropriate amount of synthetic products, add them to the organic solvent, shake slightly, and observe the dissolution of the substance.
2. Results and Discussion
2.1 The effect of the amount of pyridine (solvent)
Effects of different amounts of pyridine on the morphology of hydroxypropylmethylcellulose acetate and hydroxypropylmethylcellulose propionate. When the amount of solvent is less, it will reduce the extensibility of the macromolecular chain and the viscosity of the system, so that the degree of esterification of the reaction system will be reduced, and the product will be precipitated as a large mass. And when the amount of solvent is too low, the reactant is easy to condense into a lump and adhere to the container wall, which is not only unfavorable for the carrying out of the reaction, but also causes great inconvenience to the treatment after the reaction. In the synthesis of hydroxypropyl methylcellulose acetate, the amount of solvent used can be selected as 150 mL/2 g; for the synthesis of hydroxypropyl methylcellulose propionate, it can be selected as 80 mL/0.5 g.
2.2 Infrared spectrum analysis
Infrared comparison chart of hydroxypropyl methylcellulose and hydroxypropyl methylcellulose acetate. Compared with the raw material, the infrared spectrogram of the product hydroxypropyl methylcellulose acetate has a more obvious change. In the infrared spectrum of the product, a strong peak appeared at 1740cm-1, indicating that a carbonyl group was produced; in addition, the intensity of the stretching vibration peak of O-H at 3500cm-1 was much lower than that of the raw material, which also indicated that -OH There was a reaction.
The infrared spectrogram of the product hydroxypropyl methylcellulose propionate has also changed significantly compared with the raw material. In the infrared spectrum of the product, a strong peak appeared at 1740 cm-1, indicating that a carbonyl group was produced; in addition, the O-H stretching vibration peak intensity at 3500 cm-1 was much lower than that of the raw material, which also indicated that a OH reacted.
2.3 Determination of degree of substitution
2.3.1 Determination of substitution degree of hydroxypropyl methylcellulose acetate
Since hydroxypropyl methylcellulose has two one OH in each unit, and cellulose acetate is a product obtained by substituting one COCH3 for H in one OH, the theoretical maximum degree of substitution (Ds) is 2.
2.3.2 Determination of degree of substitution of hydroxypropyl methylcellulose propionate
2.4 Solubility of the product
The two substances synthesized had similar solubility characteristics, and hydroxypropyl methylcellulose acetate was slightly more soluble than hydroxypropyl methylcellulose propionate. The synthetic product can be dissolved in acetone, ethyl acetate, acetone/water mixed solvent, and has more selectivity. In addition, the moisture contained in the acetone/water mixed solvent can make the cellulose derivatives more safe and environmentally friendly when used as coating materials.
3. Conclusion
(1) The synthesis conditions of hydroxypropyl methylcellulose acetate are as follows: 2.5 g of hydroxypropyl methylcellulose, acetic anhydride as the esterification agent, 150 mL of pyridine as the solvent, the reaction temperature at 110 ° C, and the reaction time 1 h.
(2) The synthesis conditions of hydroxypropyl methylcellulose acetate are: 0.5 g of hydroxypropyl methylcellulose, propionic anhydride as esterification agent, 80 mL of pyridine as solvent, reaction temperature at 110 °C, and reaction time of 2 .5 h.
(3) The cellulose derivatives synthesized under this condition are directly in the form of fine powders with a good degree of substitution, and these two cellulose derivatives can be dissolved in various organic solvents such as ethyl acetate, acetone, and acetone/water.