CN111909052B - Phthalic acid derived L-phenylalanine micromolecular gel and preparation method thereof - Google Patents
Phthalic acid derived L-phenylalanine micromolecular gel and preparation method thereof Download PDFInfo
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- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 title claims abstract description 24
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 229960005190 phenylalanine Drugs 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 6
- 238000001879 gelation Methods 0.000 title description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 238000003756 stirring Methods 0.000 claims abstract description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 9
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims abstract description 8
- -1 Boc-protected L-phenylalanine Chemical class 0.000 claims abstract description 8
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000001412 amines Chemical class 0.000 claims abstract description 6
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000012074 organic phase Substances 0.000 claims abstract description 6
- 230000001105 regulatory effect Effects 0.000 claims abstract description 6
- 238000004440 column chromatography Methods 0.000 claims abstract description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 9
- 239000005457 ice water Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 238000004809 thin layer chromatography Methods 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000011010 flushing procedure Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 150000003384 small molecules Chemical class 0.000 claims description 2
- 238000009987 spinning Methods 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 abstract description 78
- 239000002904 solvent Substances 0.000 abstract description 31
- 239000002283 diesel fuel Substances 0.000 abstract description 23
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 abstract description 14
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 abstract description 12
- 239000012188 paraffin wax Substances 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract description 5
- 230000006378 damage Effects 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 abstract description 3
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 181
- 229940057995 liquid paraffin Drugs 0.000 description 23
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 238000002329 infrared spectrum Methods 0.000 description 10
- 238000001000 micrograph Methods 0.000 description 9
- 238000001338 self-assembly Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 238000003860 storage Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 238000013461 design Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000000518 rheometry Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical compound CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003022 phthalic acids Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0052—Preparation of gels
- B01J13/0065—Preparation of gels containing an organic phase
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Colloid Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of gel materials, and particularly relates to a phthalic acid-derived L-phenylalanine micromolecular gel and a preparation method thereof, which are implemented according to the following steps: (1) Adding Boc-protected L-phenylalanine, HOBt, long chain amine and NEt into a flask 3 After that, the mixture was stirred with dry dichloromethane, EDCl was added dropwise under ice bath, and after the reaction was completed, saturated Na was used 2 CO 3 The pH of the solution is regulated to be acidic; (2) concentrating the extracted organic phase, and separating by column chromatography; (3) TFA and dichloromethane are added into the obtained product to dissolve and stir; (4) Extracting, spin drying, adding phthalic anhydride, dissolving and stirring with acetone, and recrystallizing to obtain the target product. The invention has higher mechanical strength, can effectively balance or avoid the combination or damage capability of the proton solvent in the solvent to the gel, and can be used for diesel oil, paraffin, dodecane, tetradecane and the likeThe nonpolar organic solvents such as hexadecane have good gel ability.
Description
Technical Field
The invention belongs to the field of gel materials, and particularly relates to a phthalic acid-derived L-phenylalanine micromolecular gel and a preparation method thereof. The invention can be selectively gelled in non-polar solvents such as decane, dodecane, tetradecane, hexadecane, diesel oil, liquid paraffin and the like, and the gel performance is optimized by changing the chain length of a carbon chain and a substituent group.
Background
The small molecular organic gel is a special dispersion system, and gel factors are mutually entangled in a large amount of medium (liquid or gas) through self-assembly to form a space reticular structure; is a soft solid material with dominant storage modulus between solid and liquid. Small molecule organogels can produce a sensitive response to external stimuli such as force, light, PH, temperature, acoustic waves, etc. The discovery and design of a new small molecular organic gel is a rapidly developed research field, especially because the new small molecular organic gel may have wide practical application in the aspects of materials and carriers for drug controlled and sustained release, and has wide development prospects in the aspect of treating chemical pollution.
The main influencing factors of gel formation are molecular structure, intermolecular hydrogen bonds, pi-pi stacking and other molecular interactions and solvent effects of the small molecular organogel. In addition, long chain alkanes at the molecular terminals can be used to regulate their solubility and introduce van der Waals forces into the system, increasing gel performance. While the self-assembly process is largely dependent on the structure of the solvent, this suggests that specific solvent molecules may promote self-assembly of the gelator into a gel in the system.
The nature and the kind of the solvent have great influence on the self-assembly form or molecular recognition of the gel, but small molecular organic gel is easily damaged by a single factor, the mechanical strength and the performance of the small molecular organic gel are influenced, and weak interaction force among molecules and the arrangement mode of molecular structure configuration or aggregation state cannot be regulated and controlled through the directional design of a molecular structure.
Disclosure of Invention
The invention aims to provide a phthalic acid-derived L-phenylalanine micromolecular gel and a preparation method thereof. The invention has higher mechanical strength, and can effectively balance or avoid the combination or damage capability of the proton solvent in the solvent to gel by introducing the phenylalanine structure into the gel structure so as to further increase pi-pi stacking weak acting force, and has good gel capability to non-polar organic solvents such as diesel oil, paraffin, dodecane, tetradecane, hexadecane and the like.
In order to solve the technical problems, the invention is realized as follows:
the structural formula of the phthalic acid-derived L-phenylalanine small molecule gel is as follows:
as a preferable scheme, the preparation method of the phthalic acid-derived L-phenylalanine micromolecular gel can be implemented according to the following steps:
(1) Adding Boc-protected L-phenylalanine, HOBt, long chain amine and NEt into a flask 3 After the completion of the dropwise addition of EDCl in an ice bath, the ice water bath was removed and the reaction was completed with saturated Na 2 CO 3 The pH of the solution is regulated to be acidic;
(2) Concentrating the extracted organic phase, and separating by column chromatography;
(3) Adding TFA and dichloromethane into the product obtained in the step (2), dissolving and stirring, and adjusting the pH to be weak alkaline after the reaction is finished;
(4) Extracting, spin drying, adding phthalic anhydride, dissolving and stirring with acetone, and recrystallizing to obtain the target product.
Further, in step (1) of the present invention, the Boc-protected L-phenylalanine, HOBt, long chain amine, NEt 3 The molar ratio to EDCI is 1:1.2:1.2:2.2:1.2 in sequence.
Further, in the step (2) of the present invention, saturated Na is used before the separation by column chromatography 2 CO 3 The pH of the solution is regulated to 2-3.
Further, in the step (1), dripping the mixture into EDCI slowly in an ice water bath at the temperature of 0 ℃, removing the ice water bath after dripping, and stirring overnight at normal temperature.
Further, in the step (3) of the present invention, after TFA is added, the pH is adjusted to about 8 to 10 with 1mol/L HCl solution.
Further, in the step (4) of the present invention, during the recrystallization operation, acetone is used for dissolving, and then the solution is slowly dropped into petroleum ether to precipitate a white solid, and after the solution is changed into a milky suspension, the washing and drying are performed.
Compared with the prior art, the invention has the following characteristics:
1. the invention develops and designs a series of phthalic acid-derived L-phenylalanine micromolecular gel which has good gel capability on non-polar organic solvents such as diesel oil, paraffin, dodecane, tetradecane, hexadecane and the like.
2. The gel factor P with the carbon chain length of 6 6 Gel formation in diesel oil and hexadecane is impossible, and the gel factor P with the carbon chain length of 8-12 8 ～P 12 Stable gels can be formed in diesel, paraffin, dodecane, tetradecane, and hexadecane.
3. The invention has the best gel capability by testing the lowest gel concentration of all the synthesized gel agents, and the gel factor with the carbon chain length of 8.
4. According to the invention, through Scanning Electron Microscope (SEM) tests on diesel oil gel and hexadecane gel, the gel factors are self-assembled into a compact sheet-shaped or fibrous three-dimensional structure, and the solvent can be tightly wrapped in the gel factors, so that the solvent loses fluidity, and stable gel is formed.
5. The invention uses the gel factor and the infrared absorption spectrum test in diesel oil, liquid paraffin and hexadecane gel to test the P 8 After gel is formed in diesel oil, liquid paraffin and hexadecane, N-H and carbonyl characteristic absorption peaks on an amide bond are obviously red shifted. P (P) 10 And P 12 After gel is formed in three solvents, N-H and carbonyl characteristic absorption peaks on amide bonds of gel factors also generate red shift phenomena with different degrees, which indicates that intermolecular hydrogen bonds are formed between amide bonds in gel factor molecules after gel is formed, and the stretching vibration amplitude of the two is restrained, so that infrared characteristic absorption peaks are offset, and meanwhile, the hydrogen bonds can be proved to be the main driving force in the process of forming gel self-assembly.
6. The invention tests rheological property, gel factor P 8 The gel formed in diesel oil, paraffin wax and hexadecane has relatively high storage modulus, which indicates that the gel formed by the gel has higher mechanical strength and better gel effect.
7. The invention provides a design concept: by introducing phenylalanine structure into the gel structure, pi-pi stacking weak acting force is further increased, and the binding or destruction capability of proton solvent in the solvent to gel is effectively balanced or avoided. And a series of novel valuable gels were prepared.
Drawings
The invention is further described below with reference to the drawings and the detailed description. The scope of the present invention is not limited to the following description.
FIG. 1-1 shows the P of the present invention 8 Diesel oil gel; FIGS. 1-2 illustrate the P of the present invention 10 Diesel oil gel; FIGS. 1-3 illustrate the P of the present invention 12 Diesel oil gel;
FIG. 2-1 shows the P of the present invention 8 Hexadecane gel; FIG. 2-2 shows the P of the present invention 10 Hexadecane gel; FIGS. 2-3 illustrate the P of the present invention 12 Hexadecane gel;
FIG. 3-1 shows the P of the present invention 8 Liquid paraffin gel; FIG. 3-2 shows the P of the present invention 10 Liquid paraffin gel; FIGS. 3-3 illustrate the P of the present invention 12 Liquid paraffin congealsGlue;
FIG. 4-1 shows the P of the present invention 8 Diesel xerogel scanning electron microscope images; FIG. 4-2 shows the P of the present invention 10 Diesel xerogel scanning electron microscope images; FIGS. 4-3 illustrate the P of the present invention 12 Diesel xerogel scanning electron microscope images;
FIG. 5-1 shows the P of the present invention 8 Hexadecane xerogel scanning electron microscope images; FIG. 5-2 shows the P of the present invention 10 Hexadecane xerogel scanning electron microscope images; FIGS. 5-3 illustrate the P of the present invention 12 Hexadecane xerogel scanning electron microscope images;
FIG. 6-1 shows the P of the present invention 6 Gel and infrared spectrogram of gel formed by the gel; FIG. 6-2 shows the P of the present invention 8 Gel and infrared spectrogram of gel formed by the gel; FIGS. 6-3 illustrate the P of the present invention 10 Gel and infrared spectrogram of gel formed by the gel; FIGS. 6-4 illustrate the P of the present invention 12 Gel and infrared spectrogram of gel formed by the gel;
FIG. 7 shows a gel P according to the invention 8 Diesel fuel gel, P 10 Diesel fuel gel, P 12 Rheological profile of diesel gel;
FIG. 8 shows a gel P according to the invention 8 Hexadecane gel, P 10 Hexadecane gel, P 12 Rheological profile of hexadecane gel;
FIG. 9 shows a gel P according to the invention 8 Liquid paraffin gel, P 10 Liquid paraffin gel, P 12 Rheology profile of liquid paraffin gel;
FIG. 10 shows F-P respectively according to the present invention 8 Gel effect profile formed in diesel, hexadecane and paraffin;
FIG. 11-1 shows F-P according to the present invention 8 Diesel xerogel scanning electron microscope images; FIG. 11-2 shows F-P according to the present invention 8 Hexadecane xerogel;
FIG. 12 shows the gel factor F-P of the present invention 8 And infrared spectra of gels formed in diesel, hexadecane and liquid paraffin.
Detailed Description
Example 1 phthalic acid derived amino acid gelators of different chain lengths
The first step: 10mmol of Boc-protected L-phenylalanine and 1.2eq of HOBt are weighed into a round bottom flask, and 20mL of dry dichloromethane is added and stirred; 1.2eq of long-chain amine and 2.2eq of triethylamine are measured by a syringe and added into a round-bottom flask continuously to be stirred and dissolved; after the reaction system was dissolved, 1.2eq of EDCI was weighed and transferred to a small beaker, and 5mL of dry dichloromethane was added; and (3) placing the dissolved reaction system in an ice water bath at the temperature of 0 ℃, slowly dropwise adding EDCI into the reaction system, removing the ice water bath after dropwise adding, and stirring overnight at normal temperature. After the completion of the reaction, a proper amount of water is added into the system after the completion of the reaction by the thin layer chromatography, the pH is regulated to be about 2-3 by using 1mol/L HCl solution, the mixture is transferred to a separating funnel and extracted for 3 times by using dichloromethane, and the organic phase is concentrated and dried by spin-drying, and the amide product is obtained by column chromatography separation.
And a second step of: and (3) placing the product obtained by the reaction separation in the first step into a round-bottom flask, adding 16mL of dichloromethane, stirring and dissolving, adding 4mL of trifluoroacetic acid into the system after dissolving, stirring and reacting for 2-3 hours at normal temperature, and removing the protecting group. After the completion of the reaction, a proper amount of water was added to the system by thin layer chromatography, followed by Na 2 CO 3 The solution was adjusted to a pH of about 8 to 10, transferred to a separatory funnel, extracted 3 times with dichloromethane, and the organic phase was concentrated to dryness.
And a third step of: and (3) placing the product obtained in the second step into a round-bottom flask, adding 40mL of acetone, stirring and dissolving, weighing 1eq of phthalic anhydride, adding the phthalic anhydride into a reaction system, stirring and reacting for 6 hours at normal temperature, directly spinning the reaction solution after the reaction is monitored by thin-layer chromatography, and recrystallizing and separating to obtain a final product.
The recrystallization operation method comprises the following steps: taking a 500mL round-bottom flask, adding 400mL petroleum ether and stirring; adding a small amount of acetone into the product obtained by the spin-drying reaction in the third step, slowly dripping the product into 400mL of petroleum ether after the product is completely dissolved, and precipitating a large amount of white solid in a flask at the moment, wherein the solution is changed into milky suspension; after the dripping is finished, carrying out suction filtration, flushing a filter cake with petroleum ether for three times, and drying to obtain the final gel.
(one) detection results
Table 1 tests six gel factors P obtained by synthesis 6 ～P 16 Gel properties in different solvents and minimum gel concentration to form gel, the test found a gel factor P with a carbon chain length of 6 6 Gel formation in diesel and hexadecane is impossible, and the gel factor P with the carbon chain length of 8-16 8 ～P 16 Can form stable gel in diesel oil, liquid paraffin, dodecane, tetradecane and hexadecane, as shown in figures 1, 2 and 3, and P 8 With a relatively low minimum gel concentration in several solvents, the results demonstrate that the length of the carbon chain in the gel structure has a very important effect on whether gel formation is possible.
Table 1: gel properties and minimum gel concentration MGC (% wt/vol) of gels P having different hydrophobic chain lengths in various solvents
P＝precipitation；S＝soluble；I＝insoluble.
In order to visually observe the morphology of the gel formed by the gel factor in the solvent, the formed diesel gel and hexadecane gel were subjected to Scanning Electron Microscope (SEM) tests, and the test results are shown in fig. 4 and 5. From the obtained scanning electron microscope image, the gel factors can be clearly observed to self-assemble into a compact sheet-shaped or fiber-shaped three-dimensional structure, and the solvent can be tightly wrapped in the three-dimensional structure, so that the solvent loses fluidity and stable gel is formed.
To further explain the gel formation process, the gel factor and its infrared absorption spectrum in diesel, liquid paraffin and hexadecane gels were measured (see fig. 6). At gel factor P 6 In the infrared spectrum of the sample, the N-H stretching vibration peak on the amide bond is 3341cm -1 The carbonyl stretching vibration peak is 1653cm -1 In the IR spectrum in paraffin gel we can see N-H stretching vibration peak on amide bond at 3291cm -1 The carbonyl stretching vibration peak is 1642cm -1 After gel formation, the N-H and carbonyl characteristic absorption peaks on the amide bond are obviously red shifted; at gel factor P 8 In the infrared spectrum of the sample, an N-H stretching vibration peak on an amide bond of 3316cm can be observed -1 The carbonyl stretching vibration peak is 1658cm -1 At P 8 In the infrared spectrum of the diesel gel, N-H stretching vibration peak on an amide bond can be observed to be 3290cm -1 At the position, the carbonyl stretching vibration peak is 1642cm -1 A place; at P 8 In the infrared spectrum of the liquid paraffin gel, we can see that the N-H stretching vibration peak on the amide bond is 3293cm -1 The carbonyl stretching vibration peak is 1641cm -1 A place; at P 8 In the infrared spectrum of hexadecane gel, N-H stretching vibration peak on amide bond is 3292cm -1 At the position, the carbonyl stretching vibration peak is 1642cm -1 A place; p (P) 8 After gel is formed in diesel oil, liquid paraffin and hexadecane, N-H and carbonyl characteristic absorption peaks on an amide bond are obviously red shifted. Similarly, P 10 And P 12 After gel is formed in three solvents, N-H and carbonyl characteristic absorption peaks on amide bonds of gel factors also generate red shift phenomena with different degrees, which indicates that intermolecular hydrogen bonds are formed between amide bonds in gel factor molecules after gel is formed, and the stretching vibration amplitude of the two is restrained, so that infrared characteristic absorption peaks are offset, and meanwhile, the hydrogen bonds can be proved to be the main driving force in the process of forming gel self-assembly.
Rheological properties are important parameters for exploring creep properties of materials, while rheological data of organogels are very important in practical applications, and can show mechanical strength of gel materials. FIGS. 7 to 9 show the gelling agent P 6 ～P 12 Amplitude and frequency scan results for gel formation in diesel, liquid paraffin and hexadecane.
The curve shows the change trend of the storage modulus G 'and the loss modulus G' under the amplitude scanning that the frequency is fixed at 1Hz and the stress change is 0.01% -100%, when the storage modulus G 'is larger than the loss modulus G', the system shows the solid characteristic, and the deformation of the system causes energy loss along with the increase of the strain degreeThe loss modulus G "is greater than the storage modulus G' and the system exhibits rheological properties of a liquid. P can be observed from the change of the intersecting curves in the figure 6 ～P 12 The gels formed by the four gel agents in the diesel oil, the liquid paraffin and the hexadecane 3 solvents all show the change of the rheological performance from solid to liquid; the test curve G' is always greater than G "at a constant strain of 0.05% rad/s with varying frequency, which corresponds to the rheological properties of the gel solids. The amplitude sweep and the frequency sweep result indicate P 6 ～P 12 The four gel agents form true gel in diesel oil, liquid paraffin and hexadecane, and the gel has strong stability. Gel factor P 8 The gel formed in diesel oil, paraffin wax and hexadecane has relatively high storage modulus, which indicates that the gel formed by the gel has higher mechanical strength and better gel effect.
Investigation of the influence of different substituents on gel Properties
Gel factor with different substituent
From the results of the investigation of the carbon chain length to the gel performance, we know that the gel factor P with the carbon chain length of 8 8 The diesel oil, liquid paraffin and hexadecane have the smallest gel concentration and the strongest gel strength, so on the basis of the carbon chain length of 8, the influence of the substituent changing the para position of the L-phenylalanine on the gel effect and the gel performance is also explored. The synthetic route is as follows:
(II) detection results
Table 2 tests 5 gel factors OH-P obtained by synthesis 8 、Me-P 8 、OMe-P 8 、F-P 8 、Cl-P 8 Whether gel formation and minimum gel concentration of gel formation in various solvents were possible was found to be the gel factor F-P synthesized with the L-phenylalanine substrate para to F 8 Can be used in diesel oil, liquid paraffin, dodecane and tetradecaneGel formation in 6 solvents of hexadecane, while none of the other four gel factors formed gel in the solvents shown. The results also show F-P 8 Minimum gel concentration MGC and P in three solvents of diesel oil, liquid paraffin and hexadecane 8 The (phenylalanine para-position has no substituent and is H) numerical values are very close. We envision that it is possible that F-P is caused by the atomic radius of F atoms being similar to the atomic radius of H atoms 8 Can form gel in three solvents and is combined with P 8 Having similar minimum gel concentrations, the other four substituents do not have a way to form a gel because the atomic radius and steric hindrance of the groups are too large to allow better self-assembly between the gelators.
Table 2: gel characteristics of gelators with different substituents in various solvents and minimum gel concentration MGC (% wt/vol)
G＝gel；P＝precipitation；S＝soluble；I＝insoluble.
Also in order to be able to visually observe the gel factor F-P 8 Morphology of gel formed in solvent, F-P 8 The diesel gel and hexadecane gel were subjected to Scanning Electron Microscope (SEM) test, and the test results are shown in fig. 2. From the obtained scanning electron microscope image, the gel factors can be clearly observed to self-assemble into a compact sheet-shaped or fiber-shaped three-dimensional structure, and the solvent can be tightly wrapped in the three-dimensional structure, so that the solvent loses fluidity and stable gel is formed.
Gel factor F-P 8 In the infrared spectrum of (C), the N-H stretching vibration peak on the amide bond is 3317cm -1 At the position, the carbonyl stretching vibration peak is 1658cm -1 Gel F-P 8 In the infrared spectrum of the diesel gel, an N-H stretching vibration peak on an amide bond can be observed to be 3293cm -1 Where, relative to the gel F-P 8 Red shifted by 34cm -1 The carbonyl stretching vibration peak is 1641cm -1 Where, relative to F-P 8 Red shifted by 17cm -1 The N-H and carbonyl characteristic absorption peaks on the amide bond after gel formation are both significantly red shifted. Similarly, the gel factor F-P 8 In the infrared spectra of hexadecane and liquid paraffin gel, N-H and carbonyl characteristic absorption peaks on the amide bond of the gel factor also generate red shift phenomena with different degrees, and the result also shows that intermolecular hydrogen bonds are formed between amide bonds in the gel factor molecules after gel formation, and the stretching vibration amplitude of the hexadecane and liquid paraffin gel is restrained, so that the infrared characteristic absorption peaks are deviated, and meanwhile, the hydrogen bonds can be proved to be the main driving force for forming gel self-assembly.
The gel factor F-P can be observed from the curve change in the graph under the amplitude scanning with the frequency fixed at 1Hz and the stress change between 0.01% and 100% 8 The gels formed in all 3 solvents showed a change in solid to liquid rheology; the test curve G' is always greater than G "at a constant strain of 0.05% rad/s with varying frequency, which corresponds to the rheological properties of the gel solids. The results of the amplitude scan and the frequency scan show that the gel factor F-P 8 The gel is truly formed in diesel oil, hexadecane and liquid paraffin, and has strong stability.
It should be understood that the foregoing detailed description of the present invention is provided for illustrating the present invention and is not limited to the technical solutions described in the embodiments of the present invention, and those skilled in the art should understand that the present invention may be modified or substituted for the same technical effects; as long as the use requirement is met, the invention is within the protection scope of the invention.
Claims (2)
1. The phthalic acid-derived L-phenylalanine small molecule gel is characterized by having the following structural formula:
2. the method for preparing the phthalic acid derived L-phenylalanine based small molecule gel according to claim 1, comprising the following steps:
(1) 10mmol of Boc-protected L-phenylalanine and 1.2eq of HOBt are weighed into a round bottom flask, and 20mL of dry dichloromethane is added and stirred; 1.2eq of long-chain amine and 2.2eq of triethylamine are measured by a syringe and added into a round-bottom flask continuously to be stirred and dissolved; after the reaction system was dissolved, 1.2eq of EDCI was weighed and transferred to a small beaker, and 5mL of dry dichloromethane was added; putting the dissolved reaction system into an ice water bath at 0 ℃, slowly dropwise adding EDCI into the reaction system, removing the ice water bath after dropwise adding, and stirring overnight at normal temperature; adding a proper amount of water into the system after the completion of the monitoring reaction by the thin layer chromatography on the next day, adjusting the pH to 2-3 by using 1mol/L HCl solution, transferring to a separating funnel, extracting for 3 times by using dichloromethane, concentrating and spin-drying an organic phase, and separating by column chromatography to obtain an amide product;
(2) Placing the product obtained by the reaction separation in the step (1) into a round-bottom flask, adding 16mL of dichloromethane, stirring and dissolving, adding 4mL of trifluoroacetic acid into the system after dissolving, stirring and reacting for 2-3 hours at normal temperature, and removing protecting groups; after the completion of the reaction, a proper amount of water was added to the system by thin layer chromatography, followed by Na 2 CO 3 The pH value of the solution is regulated to 8-10, the solution is transferred to a separating funnel, dichloromethane is used for extraction for 3 times, and the organic phase is concentrated and dried;
(3) Placing the product obtained by the reaction in the step (2) into a round-bottom flask, adding 40mL of acetone, stirring and dissolving, weighing 1eq of phthalic anhydride, adding the phthalic anhydride into a reaction system, stirring and reacting for 6 hours at normal temperature, directly spinning the reaction solution after the reaction is monitored by thin layer chromatography, and recrystallizing and separating to obtain a final product; the recrystallization operation method comprises the following steps: taking a 500mL round-bottom flask, adding 400mL petroleum ether and stirring;
(4) Adding a small amount of acetone into the product obtained by the reaction spin-drying in the step (3), slowly dripping the product into 400mL of petroleum ether after the product is completely dissolved, and precipitating a large amount of white solid in a flask at the moment, wherein the solution is changed into milky suspension; after the dripping is finished, carrying out suction filtration, flushing a filter cake with petroleum ether for three times, and drying to obtain a final gel;
wherein, the structure of the Boc-protected L-phenylalanine is as follows:
wherein R is F;
wherein the structure of the long chain amine is as follows:
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