CN1120164C - 5-benzyloxy-trimethylene carbonate and its prepn. - Google Patents
5-benzyloxy-trimethylene carbonate and its prepn. Download PDFInfo
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- CN1120164C CN1120164C CN 01114284 CN01114284A CN1120164C CN 1120164 C CN1120164 C CN 1120164C CN 01114284 CN01114284 CN 01114284 CN 01114284 A CN01114284 A CN 01114284A CN 1120164 C CN1120164 C CN 1120164C
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- benzyloxy
- trimethylene carbonate
- glycerine
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Abstract
The present invention discloses 5-benzyloxy-trimethylene carbonate and a preparation method thereof. The present invention takes glycerol as raw material, and an intermediate of the 5-benzyloxy-trimethylene carbonate is prepared by the selective protection. The 5-benzyloxy-trimethylene carbonate is a cyclic carbonate monomer containing functionalization groups. The physical, chemical and biological properties of corresponding polycarbonate can be changed by changing functional groups of cyclic monomers. Medicaments can be introduced to monomers by a covalent bond form. Thus, the present invention provides bases for further developing biologic degrading polycarbonate and a copolymer thereof.
Description
The present invention relates to 5-benzyloxy-trimethylene carbonate and preparation method thereof, belong to organic chemistry filed.
Ring-opening polymerization is one of important Polymer Synthesizing method.Common synthesising biological degradable macromolecule, as polyester, polyamino acid, polycarbonate, poly phosphate, polydioxanones etc. generally all prepare by ring-opening polymerization.In order to further develop Biodegradable high-molecular, one of important approach is exactly the cyclic monomer of design and composite structure novelty.
Aliphatic polycarbonate is the polymer of class biodegradable/absorption, it has excellent biological compatibility, certain elasticity is arranged under the body temperature condition, at controlled release drug delivery system, there are extensive studies and application (a.Zhu K.J in aspects such as material implanted and soft tissue repair material as bio-medical material; Et al, Macromolecules, 1991,24,1736.b.Shieh S.J.; Et al, J.Biomed.Mater.Res., 1990,24,789).Yet as drug controlled release material, poly-(trimethylene carbonate) degradation in vivo speed of traditional aliphatic polycarbonate is slow, and the residence time is long, thereby is necessary to improve its degradation speed.Method of regulating the polymer degradation speed commonly used has the wetting ability that improves polymkeric substance, by the preparation multipolymer material is carried out modification etc.In recent years, about the existing more report (Vandenberg, E.J.et al, Macromolecules, 1999,32,3613) of research of the degradation speed that improves aliphatic polycarbonate.
The used monomer of aliphatic polycarbonate ring-opening polymerization generally is five-membered ring or six membered ring carbonic ether, but during owing to the ring-opening polymerization of five-membered ring carbonic ether, always having more or less has the decarbonation phenomenon to produce, and therefore, generally uses the six membered ring carbonic ether during ring-opening polymerization polycarbonate synthesis.
But cyclic monomer synthetic significant in practice that contains the functionalization side group.It is by ring-opening polymerization and subsequent reactions, medicine or other biological active substance can be introduced polymkeric substance with the form of covalent linkage, form the polymer drug system, and by other modifications, can obtain different hydrophilic/hydrophobic performance, the polymer of physical and mechanical properties and degradation characteristic, its research and application are subjected to people's pay attention to day by day.(John，G.；J.Polym.Sci.Part?A.Polym.Chem.1997，35，1901)。
The objective of the invention is synthetic a kind of new six membered ring carbonate monomer that contains functional group: the 5-benzyloxy-trimethylene carbonate, by changing the functional group on the cyclic monomer, can change physics, the chemistry and biology character of corresponding polycarbonate, and medicine can be introduced monomer with the covalent linkage form, thereby lay a good foundation for further developing biodegradable polycarbonate and multipolymer thereof.
Be the technical measures that realize that above-mentioned purpose of the present invention is taked:
The 5-benzyloxy-trimethylene carbonate, its structural formula is:
The present invention also provides the preparation method of 5-benzyloxy-trimethylene carbonate, and with 5-hydroxyl-1,3-benzal glycerine and benzyl chlorine are under alkaline condition, and 50～65 ℃ of reactions make 5-benzyloxy-1,3-benzal glycerine; 5-benzyloxy-1, the hydrolysis under acidic conditions of 3-benzal glycerine makes 2-benzyloxy-1, ammediol; 2-benzyloxy-1, ammediol and Vinyl chloroformate are catalyzer with triethylamine or pyridine, react down at-10～25 ℃ to make the 5-benzyloxy-trimethylene carbonate.5-hydroxyl-1,3-benzal glycerine can be made by glycerine and phenyl aldehyde condensation reaction, also can directly use the commercially available prod.
Above-mentioned 5-hydroxyl-1,3-benzal glycerine and benzyl chlorine react under the phase-transfer catalyst effect, can improve speed of response and productive rate greatly, and catalyst system therefor is quaternary amine or crown ether.
Above-mentioned 5-benzyloxy-trimethylene carbonate also can be directly with 2-benzyloxy-1 of the prior art, and ammediol and Vinyl chloroformate are raw material, are catalyzer with triethylamine or pyridine, reacts down at-10～25 ℃ to make the 5-benzyloxy-trimethylene carbonate.
5-benzyloxy-trimethylene carbonate fusing point is 142 ℃, measures through micro-fusing point instrument.Molecular weight is 208, measures through mass spectrograph (MS).
The structure of 5-benzyloxy-trimethylene carbonate is through infrared spectra (FT-IR), proton NMR spectrum (
1HNMR), carbon-13 nmr (
13CNMR) confirm.
Adopt the beneficial effect that the present invention reached:
The present invention also can be directly with 2-benzyloxy-1 of the prior art from glycerine, and ammediol is the six membered ring carbonate monomer that raw material has designed and synthesized a kind of novel structure first, i.e. 5-benzyloxy-trimethylene carbonate.The structure of compound is through infrared spectra (FT-IR), proton NMR spectrum (1HNMR), and carbon-13 nmr (13CNMR) is confirmed.The synthetic cyclic monomer can be used for the ring-opening polymerization of polycarbonate, and by changing the functional group on the cyclic monomer, can carry out modification to physics, the chemistry and biology character of corresponding polymer, and medicine can be introduced monomer with the covalent linkage form, thereby lay a good foundation for further developing biodegradable polycarbonate and multipolymer thereof.
The 5-benzyloxy-trimethylene carbonate that the present invention makes also has following purposes:
1, is used to prepare the monomer of biodegradable polycarbonate, can improves the physical and mechanical properties of corresponding polycarbonate, improve the second-order transition temperature of polycarbonate.
2, be used to prepare the monomer of biodegradable Copolycarbonate, can with other cyclic monomers, as glycollide, rac-Lactide, caprolactone, trimethylene carbonate, 5,5-dimethyl-trimethylene carbonate, 1,4-dioxane ketone and annular phosphate carry out ring-opening copolymerization, expand kind of polycarbonate and uses thereof.
But 3, be used to prepare the intermediate of band functionalization cyclic carbonate and polycarbonate, modify by surface then, can improve the physical and chemical performance and the surface properties of polycarbonate polycarbonate.
4, be used to prepare the intermediate of the cyclic carbonate of matters of containing biological activities, thus preparation polymer drug system.
5, be used to prepare star-like, the intermediate of tree type polycarbonate.
The invention will be further described below in conjunction with embodiment.
Embodiment one:
5-benzyloxy-1, the preparation of 3-benzal glycerine: with 45 gram 5-hydroxyls-1,3-benzal glycerine; 47.5 gram benzyl chlorine; 20 gram sodium hydroxide and 2.0 gram hexadecyl trimethyl ammonium bromide join in 500 milliliters of round-bottomed bottles, add 350 milliliters of anhydrous tetrahydro furans again, under argon shield, induction stirring; back flow reaction 48 hours; steaming desolventizes, and thick product is used twice of ethyl alcohol recrystallization then with distilled water wash (500 milliliters * 3); get white needle-like crystals 64.4 grams, productive rate 96%.Fusing point 75-76 ℃
Embodiment two:
5-benzyloxy-1, the preparation of 3-benzal glycerine: with 45 gram 5-hydroxyls-1,3-benzal glycerine; 47.5 gram benzyl chlorine; 20 gram sodium hydroxide and 2.0 gram benzos, 15 hats-five join in 500 milliliters of round-bottomed bottles, add 350 milliliters of anhydrous tetrahydro furans again, under argon shield, induction stirring; back flow reaction 48 hours; steaming desolventizes, and thick product is used twice of ethyl alcohol recrystallization then with distilled water wash (500 milliliters * 3); get white needle-like crystals 60.1 grams, productive rate 89%.Fusing point 75-76 ℃
Embodiment three:
5-benzyloxy-1, the preparation of 3-benzal glycerine: with 45 gram 5-hydroxyls-1,3-benzal glycerine; 47.5 gram benzyl chlorine; 20 gram sodium hydroxide and 2.0 gram four butyl bromation amines join in 500 milliliters of round-bottomed bottles, add 350 milliliters of anhydrous tetrahydro furans again, under argon shield, induction stirring; back flow reaction 48 hours; steaming desolventizes, and thick product is used twice of ethyl alcohol recrystallization then with distilled water wash (500 milliliters * 3); get white needle-like crystals 56.5 grams, productive rate 84%.75～76 ℃ of fusing points
Embodiment four:
5-benzyloxy-1, the preparation of 3-benzal glycerine: with 45 gram 5-hydroxyls-1,3-benzal glycerine; 47.5 gram benzyl chlorine; 20 gram sodium hydroxide join in 500 milliliters of round-bottomed bottles, add 350 milliliters of anhydrous tetrahydro furans again, under argon shield, induction stirring; back flow reaction 48 hours; steaming desolventizes, and thick product is used twice of ethyl alcohol recrystallization then with distilled water wash (500 milliliters * 3); get white needle-like crystals 31.8 grams, productive rate 47%.Fusing point 75-76 ℃.
Above-mentioned 5-hydroxyl-1,3-benzal glycerine can be made by glycerine and phenyl aldehyde condensation reaction, also can directly use the commercially available prod.
Embodiment five:
2-benzyloxy-1, the preparation of ammediol: with 54 gram 5-benzyloxies-1,3-benzal glycerine is dissolved in 200 ml methanol and the 200 milliliters of hydrochloric acid (1M), reflux 2 hours, stopped reaction.Question response cooling back adds sodium hydroxide, and to adjust pH value be 7, and concentration of reaction solution to 200 milliliter is used ethyl acetate extraction (200 * 3), and organic layer spends the night with anhydrous magnesium sulfate drying.The filtering siccative, steaming desolventizes, and thick product underpressure distillation under oil pump gets 2-benzyloxy-1, ammediol, productive rate 98%, B.p.110 ℃/6.7Pa.
Embodiment six:
The preparation of 5-benzyloxy-trimethylene carbonate: with 36.4 gram 2-benzyloxies-1, ammediol and 48.3 gram Vinyl chloroformates are dissolved in 600 milliliters of anhydrous tetrahydro furans, ice bath cooling slowly drips 45 gram triethylamines under induction stirring, allow be reflected under the ice bath (0～5 ℃) reaction 30 minutes, naturally being warming up to room temperature reacted two hours again, the filtering triethylamine hydrochloride, filtrate concentrates, thick product re-crystallizing in ethyl acetate three times, get white crystal 28.3 grams, productive rate 68%.Fusing point 142-143 ℃, molecular weight (M+) 208, ir data: 1748cm
-1Proton NMR spectrum (
1HNMR): (CDCl
3, ppm) (=7.15-7.21 (m, 5H, C
6H
5), 4.61-4.69 (m, 2H, O-CH
2-Ph), 4.21-4.32 (m, 4H, O-CH
2-CH) 3.80-3.90 (m, 1H ,-CH-CH
2) MS:m/z 208
Embodiment seven:
The preparation of 5-benzyloxy-trimethylene carbonate: with 36.4 gram 2-benzyloxies-1, ammediol and 48.3 gram Vinyl chloroformates are dissolved in 600 milliliters of anhydrous tetrahydro furans, ice bath cooling slowly drips 45 gram triethylamines under induction stirring, allow be reflected at cryosel and bathe (10 ℃) reaction down 30 minutes, naturally being warming up to room temperature reacted two hours again, the filtering triethylamine hydrochloride, filtrate concentrates, thick product re-crystallizing in ethyl acetate three times, get white crystal 29.5 grams, productive rate 71%.Fusing point 142-143 ℃.
Embodiment eight:
The preparation of 5-benzyloxy-trimethylene carbonate: with 36.4 gram 2-benzyloxies-1, ammediol and 48.3 gram Vinyl chloroformates are dissolved in 600 milliliters of anhydrous tetrahydro furans, the ice bath cooling, under induction stirring, slowly drip 45 gram triethylamines, allow be reflected at room temperature (25 ℃) reaction two hours, filtering triethylamine hydrochloride, filtrate concentrates, thick product re-crystallizing in ethyl acetate three times get white crystal 18.3 grams, productive rate 44%.Fusing point 142-143 ℃.
Claims (4)
1,5-benzyloxy-trimethylene carbonate, its structural formula is:
2, the preparation method of the described 5-benzyloxy-trimethylene carbonate of claim 1, it is characterized in that: with 2-benzyloxy-1, ammediol and chloroformic acid acetate are raw material, are catalyzer with triethylamine or pyridine, react down at-10～25 ℃ to make the 5-benzyloxy-trimethylene carbonate.
3, the preparation method of the described 5-benzyloxy-trimethylene carbonate of claim 1 is characterized in that: with 5-hydroxyl-1,3-benzal glycerine and benzyl chlorine under alkaline condition, 50～65 ℃ of reactions make 5-benzyloxy-1,3-benzal glycerine; 5-benzyloxy-1,3-benzal glycerine under acidic conditions, hydrolysis makes 2-benzyloxy-1, ammediol; 2-benzyloxy-1, ammediol and chloroformic acid acetate are catalyzer with triethylamine or pyridine, react down at-10～25 ℃ to make the 5-benzyloxy-trimethylene carbonate.
4, preparation method according to claim 3 is characterized in that: 5-hydroxyl-1, and 3-benzal glycerine and benzyl chlorine react under the phase-transfer catalyst effect under alkaline condition, and catalyst system therefor is quaternary amine or crown ether.
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| CN 01114284 CN1120164C (en) | 2001-06-15 | 2001-06-15 | 5-benzyloxy-trimethylene carbonate and its prepn. |
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| CN1120164C true CN1120164C (en) | 2003-09-03 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1313427C (en) * | 2005-02-02 | 2007-05-02 | 武汉大学 | 2-allyloxy-1,3-propylene alcohol and its preparation and use |
| CN100334081C (en) * | 2005-02-02 | 2007-08-29 | 武汉大学 | 5-acrylic oxo-trimethylene carbonate and its preparation and use |
| CN101817920B (en) * | 2006-12-29 | 2011-11-23 | 中国科学院长春应用化学研究所 | Triple-bond pendant-group aliphatic poly (ester-carbonic ester) and preparation method thereof |
| CN101914085B (en) * | 2010-08-03 | 2013-01-09 | 武汉大学 | 2-methacrylamiotrimethylene carbonate, preparation method and application thereof |
| CN106749159B (en) * | 2016-11-10 | 2019-07-26 | 河南师范大学 | 5- propynyloxy base-trimethylene carbonate and its preparation method and application |
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