Accurate-sequence poly-monothioacetal and preparation method thereof
阅读说明：本技术 一种序列精确聚单硫代缩醛及其制备方法 (Accurate-sequence poly-monothioacetal and preparation method thereof ) 是由 唐本忠 秦安军 宋波 于 2021-06-22 设计创作，主要内容包括：本发明属于有机合成技术领域,公开了一种序列精确聚单硫代缩醛及其制备方法。所述序列精确聚单硫代缩醛,其结构为式I或式II,式I中R～(1)～R～(2n+1)为有机基团,R～(2n)中n为≥1的整数；式II中R～(1)～R～(2n)为有机基团,R～(2n)中n为≥1的整数。方法：以有机溶剂为反应介质,将单醇底物和酯基活化炔单体在催化剂作用下进行反应,分离出产物1；将产物1与巯基醇类单体通过催化剂作用进行反应,分离出产物2；将产物2与酯基活化炔单体在催化剂的作用下进行反应,分离出产物3；如此迭代次序增长,得到序列精确聚单硫代缩醛。本发明的方法简单,无金属催化,无需保护基团,单体简单易得,成功制备出序列精确聚单硫代缩醛。(The invention belongs to the technical field of organic synthesis, and discloses a sequence-accurate polymonosulfo acetal and a preparation method thereof. The structure of the sequence-accurate polymonosulfo acetal is shown as formula I or formula II, wherein R in formula I 1 ～R 2n+1 Is an organic radical, R 2n Wherein n is an integer of more than or equal to 1; in the formula II R 1 ～R 2n Is an organic radical, R 2n Wherein n is an integer of 1 or more. The method comprises the following steps: taking an organic solvent as a reaction medium, reacting a mono-alcohol substrate with an ester group activated alkyne monomer under the action of a catalyst, and separating a product 1; reacting the product 1 with a thiol alcohol monomer under the action of a catalyst, and separating out a product 2; reacting the product 2 with an ester group activated alkyne monomer under the action of a catalyst, and separating a product 3; the iterative sequence is increased, and the sequence-accurate polymonosulfenac acetal is obtained. The method is simple, has no metal catalysis, does not need a protective group, has simple and easily obtained monomers, and successfully prepares the precise-sequence polyMonothioacetal.)
1. A sequence-accurate polymonosulfone, characterized in that: the structure is formula I or formula II:
in the formula I, R1～R2n+1Is an organic radical, R2nWherein n is an integer of more than or equal to 1; in the formula II R1～R2nIs an organic radical, R2nWherein n is an integer of 1 or more.
2. The sequence-accurate polymonosulfone acetal of claim 1, wherein: in the formula I, R3，R5，R7，…，R2n+1Each is selected from any one of the following chemical structural formulas 1-18; r1，R2，R4，R6，…，R2nAny one of the following structural formulas 19 to 23; in the formula II R3，R5，R7，…，R2n-1Any one selected from the following chemical structural formulas 1-18; r1，R2，R4，R6，…，R2nAny one of the following structural formulas 19 to 23;
wherein m, h and k are integers of 1-20, and s and t are respectively integers of 0-20; x is selected from O or S elements; indicates the substitution position.
3. The sequence-accurate polymonosulfone acetal of claim 1, wherein: in the formula I, R3，R5，R7，…，R2n+1Independently of alkylene-CmH2m-；
In the formula II R3，R5，R7，…，R2n-1Independently of alkylene-CmH2m-。
4. The method for producing the sequence-accurate polymethioacetal according to any one of claims 1 to 3, which comprises: the method comprises the following steps:
taking an organic solvent as a reaction medium, reacting a mono-alcohol substrate with a structure shown in formula III with an ester group activated alkyne monomer with a structure shown in formula IV under the action of a catalyst, and separating a product 1; reacting the product 1 with a thiol alcohol monomer with a structure shown in formula V under the action of a catalyst, and separating a product 2; reacting the product 2 with an ester group activated alkyne monomer with a structure shown in a formula IV under the action of a catalyst, and separating a product 3; reacting the product 3 with a thiol alcohol monomer with a structure shown in formula V under the action of a catalyst, and separating a product 4; the iterative sequence is increased, and the accurate-sequence poly-monothioacetal is obtained;
R1-OH(III)；HS-R′-OH(V)；
r' and R in the structure of the sequence-accurate polymonosulfone acetal3、R5、R7、R9、…、R2n-1、R2n+1Corresponding to R' in the sequence-accurate polymonosulenacetal structure2、R4、R6、R8、…、R2n-2、R2nCorresponding;
in the process of iterative sequence growth, the former reaction in which the activated alkyne monomer participates is the same as or different from the ester group activated alkyne monomer with the structure of formula IV in the latter reaction, and the former reaction in which the thiol alcohol monomer participates is the same as or different from the thiol alcohol monomer with the structure of formula V in the latter reaction.
5. The method of preparing sequence-accurate polymonosulfoacetals as claimed in claim 4, wherein: in each step of reaction, the catalyst is more than one of triethylene diamine, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5, 7-triazabicyclo (4.4.0) dec-5-ene, 1, 3-bis (2, 6-diisopropylphenyl) imidazole-2-ene, sodium methoxide, potassium ethoxide and potassium tert-butoxide;
in each step of reaction, the organic solvent is selected from more than one of tetrahydrofuran, dichloromethane, chloroform, toluene, 1, 4-dioxane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, acetonitrile, ethanol, N-methylpyrrolidone, dimethyl carbonate, diethyl carbonate, ethylene carbonate and propylene carbonate.
6. The method of preparing sequence-accurate polymonosulfoacetals as claimed in claim 4, wherein:
in the reaction of ester group activated alkyne monomer, the amount of the catalyst is 1-40% of the molar weight of the ester group activated alkyne monomer;
in the reaction of the thiol alcohol monomer, the amount of the catalyst is 1-40% of the mole amount of the thiol alcohol monomer.
7. The method of preparing sequence-accurate polymonosulfoacetals as claimed in claim 4, wherein:
in each reaction, the amount concentration of the ester group activated alkyne monomer and the thiol alcohol monomer in the organic solvent is 0.05-5 mol/L.
8. The method of preparing sequence-accurate polymonosulfoacetals as claimed in claim 4, wherein: the molar ratio of the monoalcohol substrate with the structure of formula III to the ester group activated alkyne monomer with the structure of formula IV is (0.9-2): 1;
in the reaction of the thiol alcohol monomer, the molar ratio of the product of the previous step to the thiol alcohol monomer is 1: (1-3);
in the reaction in which the ester group activated alkyne monomer participates, the molar ratio of the product of the previous step reaction to the ester group activated alkyne monomer with the structure of formula IV is (0.9-2): 1.
9. the method of preparing sequence-accurate polymonosulfoacetals as claimed in claim 4, wherein:
the reaction temperature in each step is 0-100 ℃; the reaction time is 0.25-72 h.
10. Use of the sequence-accurate polymonosulfone acetal according to any one of claims 1 to 3, characterized in that: the sequence-accurate polymonosulfone is used in the field of information storage and/or encryption.
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a sequence-accurate polymonosulfo acetal and a preparation method thereof.
Background
Natural sequence precision macromolecules, such as DNA and RNA in our body, can be synthesized efficiently under mild (-37 ℃) conditions without protecting groups.
Inspired by natural sequence accurate macromolecules, chemists have developed various methods for preparing artificial sequence accurate macromolecules at present. The iterative index and the iterative order growing method are the two most commonly used methods. The methods that have been developed today mainly have the following disadvantages: (1) most monomers need to be carefully designed and synthesized in multiple steps, and the types of the monomers are very limited; (2) many methods require protection and deprotection strategies, take a lot of effort and time and are not in line with the principles of atomic economy; (3) some synthesis routes use metal catalysts which accumulate over multiple cycles and contaminate the product. Therefore, there is an urgent need to develop a simple and efficient method for preparing sequence-accurate macromolecules, which does not need metal catalysis, protective groups and atom economy.
Disclosure of Invention
In view of the above disadvantages and shortcomings of the prior art, the primary object of the present invention is to provide a sequence-accurate polymonosulfone. The structure and the sequence of the sequence-accurate polymonosulfone acetal can be analyzed through secondary mass spectrometry, so that the sequence-accurate polymonosulfone acetal has potential application in the fields of information storage, encryption and the like.
Another object of the present invention is to provide a process for the preparation of the above sequence-accurate polymonosulfoacetals. The preparation method can be carried out at normal temperature, and the reaction is green, efficient and easy to operate.
The purpose of the invention is realized by the following technical scheme:
a sequence-accurate polymonosulfone acetal having the structure of formula I or formula II:
in the formula I, R1～R2n+1Is an organic radical, R in the formula II1～R2nIs an organic radical, R2nWherein n is an integer of 1 or more.
Wave line representation in the Structure of formula IStructure, R' represents R3、R5、R7、R9、…、R2n-1(ii) a R' represents R2、R4、R6、R8、…、R2n-2；
Wave line representation in the Structure of formula IIStructure, R' represents R3、R5、R7、R9、…、R2n-1(ii) a R' represents R2、R4、R6、R8、…、R2n-2。
Preferably, R in formula I3，R5，R7，…，R2n+1Each is selected from any one of the following chemical structural formulas 1-18; r1，R2，R4，R6，…，R2nAny one of the following structural formulas 19 to 23; in the formula II R3，R5，R7，…，R2n-1Any one selected from the following chemical structural formulas 1-18; r1，R2，R4，R6，…，R2nAny one of the following structural formulas 19 to 23;
wherein m, h and k are integers of 1-20, and s and t are respectively integers of 0-20; x is selected from O or S elements; indicates the substitution position.
In the formula I, R3，R5，R7，…，R2n+1Independently more preferably alkylene-CmH2m-。
In the formula II R3，R5，R7，…，R2n-1Independently more preferably alkylene-CmH2m-。
The preparation method of the sequence-accurate polythioacetal comprises the following steps:
taking an organic solvent as a reaction medium, reacting a mono-alcohol substrate with a structure shown in formula III with an ester group activated alkyne monomer with a structure shown in formula IV under the action of a catalyst, and separating to obtain a product 1; reacting the product 1 with a thiol alcohol monomer with a structure shown in formula V under the action of a catalyst, and separating to obtain a product 2; reacting the product 2 with an ester group activated alkyne monomer with a structure shown in a formula IV under the action of a catalyst, and separating to obtain a product 3; reacting the product 3 with a thiol alcohol monomer with a structure shown in formula V under the action of a catalyst, and separating to obtain a product 4; the iterative sequence is increased, and the accurate-sequence poly-monothioacetal is obtained;
R1-OH (III)；HS-R′-OH (V)。
r' and R in the structure of the sequence-accurate polymonosulfone acetal3、R5、R7、R9、…、R2n-1、R2n+1Corresponding to R' in the sequence-accurate polymonosulenacetal structure2、R4、R6、R8、…、R2n-2、R2nAnd (7) corresponding.
In the process of iterative sequence growth, the ester group activated alkyne monomer with the structure of formula IV in the previous reaction and the ester group activated alkyne monomer with the structure of formula IV in the next reaction are the same or different, and the thiol alcohol monomer with the structure of formula V in the previous reaction and the thiol alcohol monomer with the structure of formula V in the next reaction are the same or different
In each step of reaction, the organic solvent is selected from more than one of tetrahydrofuran, dichloromethane, chloroform, toluene, 1, 4-dioxane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, acetonitrile, ethanol, N-methylpyrrolidone, dimethyl carbonate, diethyl carbonate, ethylene carbonate and propylene carbonate.
In each reaction, the amount concentration of the ester group activated alkyne monomer and the thiol alcohol monomer in the organic solvent is 0.05-5 mol/L independently; further preferably, the amount concentration of the ester group activated alkyne monomer and the thiol alcohol monomer in the organic solvent is 1-4 mol/L independently.
In each step of reaction, the catalyst is more than one of triethylene diamine, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5, 7-triazabicyclo (4.4.0) dec-5-ene, 1, 3-bis (2, 6-diisopropylphenyl) imidazole-2-ene, sodium methoxide, potassium ethoxide and potassium tert-butoxide.
In the reaction of the ester group activated alkyne monomer, the amount of the catalyst is 1-40% of the molar amount of the ester group activated alkyne monomer or the thiol alcohol monomer, preferably 2-5%.
In the reaction of the thiol-alcohol monomer, the amount of the catalyst is 1-40% of the molar amount of the thiol-alcohol monomer, preferably 2-5%.
The molar ratio of the monoalcohol substrate with the structure of formula III to the ester group activated alkyne monomer with the structure of formula IV is (0.9-2): 1;
in the reaction of the thiol alcohol monomer, the molar ratio of the product of the previous step to the thiol alcohol monomer is 1: (1-3).
In the reaction in which the ester group activated alkyne monomer participates, the molar ratio of the product of the previous step reaction to the ester group activated alkyne monomer with the structure of formula IV is (0.9-2): 1.
the reaction temperature in each step is 0-100 ℃, and the normal temperature is preferred; the reaction time is 0.25-72 h.
The separation steps are as follows: after the reaction of each step is finished, the product is purified by column chromatography and dried to constant weight.
The preparation method and the obtained product have the following advantages and beneficial effects:
(1) the preparation method can be carried out at normal temperature, and the monomers do not need to be prepared and synthesized in multiple steps, so that the cost is low, and the preparation method is green and environment-friendly;
(2) the preparation method of the invention has simple operation, easily obtained reaction raw materials and catalyst, and can be directly purchased or prepared by simple reaction; the reaction condition is mild, and energy is saved;
(3) the preparation method has good functional group tolerance and can introduce various groups. The structure and the sequence of the sequence-accurate polymonosulfone acetal can be analyzed through secondary mass spectrometry, so that the sequence-accurate polymonosulfone acetal has potential application in the fields of information storage, encryption (products) and the like.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the sequence-refined polymethioacetal A1-A7 in DMSO prepared in example 1 of the present invention;
FIG. 2 is an electrospray mass spectrum of the sequential precision polymethioacetal A1-A7 prepared in example 1 of the present invention;
FIG. 3 is a gel permeation chromatogram of the sequence-refined polymonosulfoacetal A1-A7 prepared in example 1 of the present invention;
FIGS. 4-10 are nuclear magnetic resonance carbon spectrograms of the sequence-refined polymethioacetal A1-A7 in DMSO prepared in example 1 of the present invention;
FIGS. 11-20 are nuclear magnetic resonance hydrogen spectra of the sequence-refined polymethioacetal B2-B11 in DMSO prepared in example 2 of the present invention;
FIGS. 21 and 22 are electrospray mass spectra of sequential precision polymethioacetals B1-B11 prepared in example 2 of the present invention;
FIG. 23 is a gel permeation chromatogram of the sequence-refined polymonosulfone B1-B11 prepared in example 2 of the present invention;
FIGS. 24-33 are nuclear magnetic resonance carbon spectrograms of the sequenced poly (monothioacetal) B1-B11 in DMSO, prepared in example 2 of the present invention;
FIG. 34 is a secondary mass spectrum of the sequence-refined polymonosulfone A7 prepared in example 1 of the present invention;
FIG. 35 is a secondary mass spectrum of the sequence-refined polymonosulfone B11 prepared in example 2 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1
A sequence-accurate polymonosulfone A7 of this example has the following formula:
the sequence-accurate polymonosulfone is prepared by reacting a monol substrate with an ester-based activated alkyne monomer in an organic solvent under the action of a catalyst, separating a reaction product, and then reacting with a thiol alcohol monomer, wherein the reaction equation is as follows:
the specific preparation steps of the sequence-refined polymonosulfone described in this example are as follows:
the method comprises the following steps: s1(12.9g,105mmol), methyl propiolate (8.9mL,100mmol), triethylenediamine (DABCO) (560mg,5mmol) and 50mL tetrahydrofuran were added to a dry Schlenk' S tube, and after reaction in air at 25 ℃ for 3 hours, the solvent was removed and the product A1 was obtained in 99% yield by column chromatography.
Step two: a1(10.3g,50mmol), mercaptoethanol (5.3mL,75mmol), 1, 3-bis (2, 6-diisopropylphenyl) imidazol-2-ene (972mg,2.5mmol) and 20mL dimethyl sulfoxide were added to a dry Schlenk's tube and after 5 hours reaction at 25 ℃ under nitrogen, extracted 3 times with ethyl acetate, the solvent was removed and isolated by column chromatography to give product A2 in 96% yield.
Replacing the product a2 for S1 in step one, and reacting according to the steps and conditions of step one to obtain product A3 (yield 98%); the product A3 was then substituted for the product A1 in step two, and the reaction was carried out according to the steps and conditions of step two to obtain the product A4 (yield 95%), which was increased in iterative order to finally obtain the polymonosulfenac A7 in an overall yield of 77%.
Sequence-accurate polythioacetal a7 characterization data: white liquid, yield 77%.
The NMR spectrum(s) (representing solvent peaks) of the sequence-refined polythioacetal A1-A7 obtained in this example is shown in FIG. 1, the electrospray mass spectrum is shown in FIG. 2, the gel permeation chromatography is shown in FIG. 3, and the NMR carbon spectrum is shown in FIGS. 4-10.
As can be seen from the NMR spectrum of FIG. 1, the NMR peaks for the C-C double bond hydrogens of A1, A3, A5 and A7 appeared at 7.61-7.68 and 5.25-5.35ppm, and the coupling constants for both groups were 12.5Hz, indicating both E configurations. The NMR peaks of hydroxyl hydrogen in A2, A4 and A6 appear at 4.85-4.76ppm, and the NMR peak of hydrogen on the carbon of monothioacetal appears at 5.03-4.87ppm, and other NMR peaks can correspond to the structures of A1-A7, which shows that the polymonosulfoxide with a definite structure is obtained.
The electrospray mass spectrum of FIG. 2 well characterizes the molecular weight information of products A1-A7.
As can be seen from the gel permeation chromatography of FIG. 3, the spectra of A1-A7 are all narrow single peaks, and all have good monodispersity and purity. FIG. 34 is a secondary mass spectrum of the sequence-refined polymonosulfone A7 prepared in example 1 of the present invention.
The above data all demonstrate that we have taken the target product. The sequence-accurate polymonosulfone acetal is easily soluble in DCM, chloroform, DMF, dimethyl sulfoxide (DMSO) and other common organic solvents at room temperature.
The structure and the sequence of A7 can be clearly resolved by secondary mass spectrometry, and the method is expected to be applied to information storage.
Example 2
A sequence-accurate polymonosulfone B11 of this example has the following structural formula:
the above-mentioned accurate sequence poly monothioacetal reacts with ester group activated alkyne monomer in organic solvent through the action of catalyst by using monoalcohol substrate, the reaction product is separated, and then reacts with thiol alcohol monomer to prepare, the reaction equation is as follows:
the specific preparation steps of the sequence-refined polymonosulfone described in this example are as follows:
the method comprises the following steps: s1(12.9g,105mmol), methyl propiolate (8.9mL,100mmol), triethylenediamine (DABCO) (560mg,5mmol) and 50mL tetrahydrofuran were added to a dry Schlenk' S tube, and after reaction in air at 25 ℃ for 3 hours, the solvent was removed and the product B1 was obtained in 99% yield by column chromatography.
Step two: after B1(4.12g,20mmol), mercaptobutanol (3.1mL,30mmol), 1, 3-bis (2, 6-diisopropylphenyl) imidazol-2-ene (389mg,1mmol) and 20mL of dimethyl sulfoxide were added to a dry schlenk tube, reacted at 25 ℃ under nitrogen for 5 hours, extracted 3 times with ethyl acetate, the solvent was removed, and separated by column chromatography to give product B2 in 95% yield.
Replacing S1 in the step one by the product B2, replacing one methyl propiolate in the step one by benzyl propiolate, and carrying out reaction according to the steps and conditions of the step one to obtain a product B3 (yield 98%); then replacing the product B1 in the second step with the product B3, replacing mercaptobutanol in the second step with mercaptoethanol, and carrying out reaction according to the steps and conditions of the second step to obtain a product B4 (yield is 99%); substituting product B4 for step one, S1, and reacting according to the steps and conditions of step one to obtain product B5 (97% yield); replacing the product B1 with the product B5 in the second step, replacing mercaptobutanol with mercaptohexanol in the second step, and carrying out the reaction according to the steps and conditions of the second step to obtain a product B6 (yield is 92%); the iterative sequence of the selection of the appropriate reaction monomers was increased to give the final polymonosulfo acetal B11 in 54% overall yield.
Sequence-accurate polymonosulfone B11 characterization data: pale green liquid, yield 54%.
The NMR spectra (x represents the solvent peak) of the sequence-refined polythioacetals B2-B11 obtained in this example are shown in FIGS. 11-20, the electrospray mass spectra are shown in FIGS. 21 and 22, the gel permeation chromatography is shown in FIG. 23, and the NMR carbon spectra are shown in FIGS. 24-33. FIG. 35 is a secondary mass spectrum of the sequence-refined polymonosulfone B11 prepared in example 2 of the present invention.
The characterization data all prove that we have taken the target product. The sequence-accurate polymonosulfone acetal is easily soluble in DCM, chloroform, DMF, dimethyl sulfoxide (DMSO) and other common organic solvents at room temperature.
The structure and the sequence of B11 can be clearly resolved by secondary mass spectrometry, and the method is expected to be applied to information storage.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.