CN111303395B - Preparation method of low molecular weight polycaprolactone - Google Patents

Abstract

The invention belongs to the technical field of polymer synthesis, and in particular relates to a preparation method of low molecular weight polycaprolactone. The method includes the following steps: S1, in a hydrocarbon solvent, using a bio-based phenol to replace the alkyl aluminum to prepare a bio-based phenol catalyst; S2, adding ε-CL and a hydrocarbon solvent into an anhydrous, oxygen-free, nitrogen-protected reactor , adding a bio-based phenol catalyst to carry out a polymerization reaction to obtain a polymer product, which is washed with ethanol to obtain a polycaprolactone product; wherein, the molecular weight of the low molecular weight polycaprolactone is 7000-40000. The invention adopts the alkyl aluminum substituted by bio-based phenol as a catalyst, has simple polymerization process, low polymerization temperature, short polymerization time, reduces energy consumption and cost, and can control the amount and structure of the bio-based phenol to regulate the polycaprolactone. Stereoregularity, thereby controlling the crystallinity, and then regulating the degradation time and degradation rate of polycaprolactone in the human body, making PCL better used in the field of drug release.

Description

A kind of preparation method of low molecular weight polycaprolactone

technical field

The invention belongs to the technical field of polymer synthesis, and in particular relates to a preparation method of low molecular weight polycaprolactone.

Background technique

In today's world, energy is over-exploited and environmental pollution is becoming more and more serious, resulting in a huge energy crisis and population crisis. And biodegradable materials can solve this series of problems very well, which makes biodegradable materials develop rapidly, such as: polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA) and so on. A few biodegradable materials can be degraded spontaneously in the human body and are completely harmless to the human body, which makes such biodegradable materials develop rapidly in the medical field, such as PLA and PCL. Among them, PCL, because of its strong hydrophobicity, can easily form copolymers with monomers with strong hydrophilicity, so that it can spontaneously form temperature-sensitive hydrogels, and the coated drug materials can be easily prepared. This kind of drug coating material can utilize the degradation properties of PCL to control the release rate and time of the drug, so as to achieve the effect of sustained drug release and long-term treatment of diseases. Therefore, PCL is widely used in the field of drug release.

When PCL is used as a drug coating material, PCL is required to be low molecular weight. However, the most mature catalyst for the preparation of PCL is Sn-based catalyst, which can adjust the amount of catalyst to change the molecular weight of PCL. However, its polymerization process is complicated and harsh, with high polymerization temperature and long polymerization time. For example, Chinese patent CN 101255234 A discloses a temperature-sensitive triblock copolymer and its preparation method and application. In the method, the minimum preparation temperature is 130° C., and the polymerization time is 3-12 hours. The higher temperature and time make the cost higher, the energy consumption is higher. At the same time, when PCL is used as a drug coating material, it is hoped that by controlling the crystallinity of PCL to control the drug release time, it can be applied to drug release materials more efficiently. However, Sn-based catalysts cannot control the stereoregularity of the polymerization product. Therefore, it is hoped to develop a new catalyst that can make the polymerization process simple under the premise of satisfying environmental protection, and can adjust the structure of the catalyst to control the polymerization product PCL. The crystallinity is better to meet the medical application of PCL.

SUMMARY OF THE INVENTION

In view of the deficiencies of the prior art, the purpose of the present invention is to provide a preparation method of low molecular weight polycaprolactone, which adopts the alkylaluminum substituted by bio-based phenol as a catalyst, the polymerization process is simple, the polymerization temperature is low, the polymerization time is short, and the Energy consumption and cost, and can control the stereoregularity of polycaprolactone by controlling the amount and structure of bio-based phenol, thereby controlling the crystallinity, and then regulating the degradation time and degradation speed of polycaprolactone in the human body, making PCL It is better used in the field of drug release.

The preparation method of low molecular weight polycaprolactone of the present invention comprises the following steps:

S1. In a hydrocarbon solvent, a bio-based phenol is used to replace the alkyl aluminum to prepare a bio-based phenol catalyst;

S2, adding ε-CL and hydrocarbon solvent into an anhydrous, oxygen-free, nitrogen-protected reactor, adding a bio-based phenol catalyst to carry out a polymerization reaction to obtain a polymer product, washing with ethanol to obtain a polycaprolactone product;

Wherein, the molecular weight of the low molecular weight polycaprolactone is 7000-40000.

In step S1, the bio-based phenol is 2-methyl-5-isopropylphenol (carvacrol), 3-pentadecylphenol (cardanol) or 2-isopropyl-5-methylphenol A type of phenol (thymol). The present invention selects three kinds of bio-based phenols for food processing, and such bio-based phenols are completely harmless to the human body and are environmentally friendly.

In step S1, the alkyl aluminum is AlR ₃ , wherein R is methyl, ethyl, n-butyl or isobutyl, preferably isobutyl.

In step S1, the molar ratio of the bio-based phenol and alkyl aluminum: M _Fen :M _Al =0.5-1.5:1. The reason for choosing this range is that within this range, the conversion rate of PCL prepared by ring-opening polymerization can be high, and the molecular weight distribution of PCL is narrow. Within this range, the steric configuration of PCL can also be adjusted by the amount of bio-based phenol to adjust the crystallinity. If it is not within this range, when its M _Fen : M _Al is small, it will lead to a violent polymerization reaction, it is difficult to control the stereo configuration of PCL, and the molecular weight distribution is wide at the same time. When M _Fen : M _Al is larger, the larger steric hindrance will reduce the insertion speed of the monomer and reduce the polymerization activity.

In step S1, the bio-based phenol is used to replace the alkyl aluminum, the reaction temperature is 0-5°C, and the reaction time is 4-6h.

In step S1 and step S2, the hydrocarbon solvent is alkane or aromatic hydrocarbon, the alkane is n-hexane or cyclohexane, and the aromatic hydrocarbon is benzene, toluene or ethylbenzene, preferably toluene.

In step S2, the concentration of the ε-CL in the hydrocarbon solvent is 1-2 mol/L.

In step S2, the molar ratio of aluminum alkyl and ε-CL in the bio-based phenol catalyst: M _Al :M _ε-CL =3:1000-50:1000.

In step S2, the polymerization reaction temperature is 60-100° C., and the polymerization reaction time is 0.1-1 h.

When step S2 is controlled under the above conditions, the conversion rate of ε-CL is relatively high, reaching more than 85%

Compared with the prior art, the beneficial effects of the present invention are:

1. The present invention adopts a bio-based phenol catalyst (a bio-based phenol-substituted alkyl aluminum) to catalyze the ring-opening polymerization of ε-CL to prepare low molecular weight polycaprolactone. Using this type of catalyst, compared with the traditional Sn-type catalyst, the polymerization temperature is lower, the polymerization time is shorter, the process is simpler, the energy consumption and cost are reduced, and it is in line with the industrial development trend.

2. Different bio-based phenols can make the molecular weight and crystallinity of the generated PCL different due to their different structures. Therefore, the spatial regularity and symmetry of the polymer product can be regulated by adjusting the structure and dosage of the bio-based phenol, so as to easily adjust the crystallinity of the polymer product to control the release time of PCL in the human body, making the application of PCL in the medical field more flexible. . The degradation rate of PCL is different with different crystallinity. This method is expected to adjust the degradation rate of PCL by changing the catalyst structure.

3. The bio-based phenol that can be used in food processing used in the present invention is extracted from plant species in nature, which is not only completely harmless to the human body, but also has a renewable source. It is in line with the current environmental protection trend, and the cost is low.

Description of drawings

Fig. 1 is the reaction mechanism diagram of bio-based phenol-substituted triisobutylaluminum catalyzed ε-CL ring-opening polymerization;

Figure 2 is the infrared spectrum of 2-methyl-5-isopropylphenol, 3-pentadecylphenol and 2-isopropyl-5-methylphenol substituted triisobutylaluminum catalyzed by ε-CL to generate PCL ;

Figure 3 is the NMR spectrum of 2-methyl-5-isopropylphenol, 3-pentadecylphenol and 2-isopropyl-5-methylphenol substituted triisobutylaluminum catalyzed by ε-CL to generate PCL .

Detailed ways

The present invention will be further described below in conjunction with the examples, but the present invention is not limited.

The experimental methods described in the following examples, unless otherwise specified, are conventional methods; if no specific techniques or conditions are indicated in the examples, the techniques or conditions described in the literature in the field or according to the product specification are carried out; The reagents and materials are all analytically pure reagents, and can be obtained from commercial sources unless otherwise specified.

See Table 1 for the manufacturer's information of the medicines used in the present invention.

Table 1 Manufacturer information of the medicines used in the present invention

drug Manufacturer Carvacrol, Cardanol, Thymol Sarn Chemical Technology (Shanghai) Co., Ltd. n-hexane, cyclohexane Sinopharm Group Chemical Reagent Co., Ltd. Benzene, Toluene, Ethylbenzene Sinopharm Group Chemical Reagent Co., Ltd. anhydrous ethanol Sinopharm Group Chemical Reagent Co., Ltd. caprolactone Shanghai Aladdin Biochemical Technology Co., Ltd. Alkyl aluminum Bailingwei Technology Co., Ltd.

Example 1

2-Methyl-5-isopropylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =0.5:1 substituted triisobutylaluminum, the configuration temperature was 0°C, and the configuration time was 6h. ε-CL and cyclohexane were placed in the reactor, so that the concentration of ε-CL was 1 mol/L, and the bio-based phenol catalyst was injected into the reactor according to M _Al :M _ε-CL =3:1000. In an oil bath at 60 °C, the reaction was carried out for 10 min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 93.6%.

Example 2

2-Methyl-5-isopropylphenol was configured as a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 2°C, and the configuration time was 5h. ε-CL and toluene were placed in the reactor, so that the concentration of ε-CL was 1.3 mol/L, and the bio-based phenol catalyst was injected into the reactor according to M _Al :M _ε-CL =5:1000, and the reactor was adjusted to 80 ℃ oil bath, the reaction 30min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 94.7%.

Example 3

2-Methyl-5-isopropylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1.5:1 substituted triethylaluminum, the configuration temperature was 4°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 1.5mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =20:1000, and set the reactor to 100 ℃ oil bath, the reaction 1h. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 96.2%.

Example 4

2-Methyl-5-isopropylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 5°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 2mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =50:1000, and set the reactor to 60 ℃ In an oil bath, the reaction was carried out for 30 min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 98.9%.

Table 2 Activity of 2-methyl-5-isopropylphenol catalyst for ring-opening polymerization of caprolactone

Example 5

3-Pentadecylphenol was prepared into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =0.5:1 substituted triisobutylaluminum, the configuration temperature was 0°C, and the configuration time was 6h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 1 mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =3:1000, and set the reactor to 60 ℃ In an oil bath, the reaction was carried out for 10 min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 91.7%.

Example 6

3-Pentadecylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 2°C, and the configuration time was 5h. ε-CL and toluene were placed in the reactor, so that the concentration of ε-CL was 1.3 mol/L, and the bio-based phenol catalyst was injected into the reactor according to M _Al :M _ε-CL =5:1000, and the reactor was adjusted to 80 ℃ oil bath, the reaction 30min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 92.1%.

Example 7

3-Pentadecylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1.5:1 substituted triisobutylaluminum, the configuration temperature was 4°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 1.5mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =20:1000, and set the reactor to 100 ℃ oil bath, the reaction 1h. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 94.2%.

Example 8

3-Pentadecylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 5°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 2mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =50:1000, and set the reactor to 60 ℃ In an oil bath, the reaction was carried out for 30 min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 96.8%.

Table 3 Activity of 3-pentadecylphenol catalyst for ring-opening polymerization of caprolactone

Example 9

2-Isopropyl-5-methylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =0.5:1 substituted triisobutylaluminum, the configuration temperature was 0°C, and the configuration time was 6h. Put ε-CL and n-hexane in the reactor, so that the concentration of ε-CL is 1 mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =3:1000, and set the reactor to 60 ℃ oil bath, the reaction 10min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 86.2%.

Example 10

2-Isopropyl-5-methylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 2°C, and the configuration time was 5h. ε-CL and toluene were placed in the reactor, so that the concentration of ε-CL was 1.3 mol/L, and the bio-based phenol catalyst was injected into the reactor according to M _Al :M _ε-CL =5:1000, and the reactor was adjusted to 80 ℃ oil bath, the reaction 30min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 88.3%.

Example 11

2-Isopropyl-5-methylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1.5:1 substituted triisobutylaluminum, the configuration temperature was 4°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 1.5mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =20:1000, and set the reactor to 100 ℃ oil bath, the reaction 1h. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion rate of 92.6%.

Example 12

2-Isopropyl-5-methylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =1:1 substituted triisobutylaluminum, the configuration temperature was 5°C, and the configuration time was 4h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 2mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =50:1000, and set the reactor to 60 ℃ In an oil bath, the reaction was carried out for 30 min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 95.3%.

Table 4 Activity of 2-isopropyl-5-methylphenol catalyst for ring-opening polymerization of caprolactone

Comparative Example 1

2-Methyl-5-isopropylphenol was configured into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =0.4:1 and 1.6:1 substituted triisobutylaluminum, and the configuration temperature was 0°C, and the configuration The time is 6h. ε-CL and cyclohexane were placed in the reactor, so that the concentration of ε-CL was 1 mol/L, and the bio-based phenol catalyst was injected into the reactor according to M _Al :M _ε-CL =3:1000. In an oil bath at 60 °C, the reaction was carried out for 10 min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 94.2% and 73.7%.

Comparative Example 2

3-Pentadecylphenol was prepared into a bio-based phenol catalyst solution according to the molar ratio: M _FEN :M _Al =0.4:1 and 1.6:1 substituted triisobutylaluminum, the configuration temperature was 0°C, and the configuration time was 6h. Put ε-CL and toluene in the reactor, so that the concentration of ε-CL is 1 mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =3:1000, and set the reactor to 60 ℃ In an oil bath, the reaction was carried out for 10 min. The polymer product was washed with ethanol and dried to obtain PCL with a conversion rate of 96.7% and 75.1%.

Comparative Example 3

2-Isopropyl-5-methylphenol is configured according to the molar ratio: M _FEN : M _Al = 0.4:1 and 1.6:1 substituted triisobutylaluminum to form a bio-based phenol catalyst solution, and the configuration temperature is 0° C. The time is 6h. Place ε-CL and n-hexane in the reactor, so that the concentration of ε-CL is 1 mol/L, inject bio-based phenol catalyst into the reactor according to M _Al :M _ε-CL =3:1000, and set the reactor to 60 ℃ oil bath, the reaction 10min. The polymerized product was washed with ethanol and dried to obtain PCL with a conversion ratio of 90.4% and 68.3%.

Table 5 Activity of three bio-based phenol catalysts for ring-opening polymerization of caprolactone at lower/higher M _FEN : M _Al

Claims (4)

1. a preparation method of low number-average molecular weight polycaprolactone, is characterized in that: may further comprise the steps: S1. In a hydrocarbon solvent, a bio-based phenol is used to replace the alkyl aluminum to prepare a bio-based phenol catalyst; S2, adding ε-CL and hydrocarbon solvent into an anhydrous, oxygen-free, nitrogen-protected reactor, adding a bio-based phenol catalyst to carry out a polymerization reaction to obtain a polymer product, washing with ethanol to obtain a polycaprolactone product; In step S1, the bio-based phenol is carvacrol, cardanol or thymol; the alkyl aluminum is AlR ₃ , wherein R is methyl, ethyl, n-butyl or isobutyl; Described molar ratio of bio-based phenol and alkyl aluminum: M _Fen : M _Al =0.5-1.5:1; described using bio-based phenol to replace alkyl aluminum, the reaction temperature is 0-5 ℃, and the reaction time is 4- 6h; In step S2, the polymerization reaction temperature is 60-100° C., and the polymerization reaction time is 0.1-1 h; wherein, the number average molecular weight of the low number average molecular weight polycaprolactone is 7000-40000. 2. the preparation method of low-number-average molecular weight polycaprolactone according to claim 1, is characterized in that: in step S1 and step S2, described hydrocarbon solvent is alkane or aromatic hydrocarbon, and alkane is n-hexane or cyclohexane Hexane, aromatic hydrocarbons are benzene, toluene or ethylbenzene. 3. The preparation method of low number-average molecular weight polycaprolactone according to claim 1, characterized in that: in step S2, the concentration of the ε-CL in the hydrocarbon solvent is 1-2 mol/L. 4. the preparation method of low-number-average molecular weight polycaprolactone according to claim 1, is characterized in that: in step S2, the mol ratio of alkylaluminum and ε-CL in the described bio-based phenol catalyst: M _Al :M _ε-CL =3:1000-50:1000.

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