[go: up one dir, main page]

CN101643450B - A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione - Google Patents

A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione Download PDF

Info

Publication number
CN101643450B
CN101643450B CN 200910092120 CN200910092120A CN101643450B CN 101643450 B CN101643450 B CN 101643450B CN 200910092120 CN200910092120 CN 200910092120 CN 200910092120 A CN200910092120 A CN 200910092120A CN 101643450 B CN101643450 B CN 101643450B
Authority
CN
China
Prior art keywords
dihydro
synthetic method
ether
solvent
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN 200910092120
Other languages
Chinese (zh)
Other versions
CN101643450A (en
Inventor
张文雄
王子涛
王杨
席振峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Peking University
Original Assignee
Peking University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Peking University filed Critical Peking University
Priority to CN 200910092120 priority Critical patent/CN101643450B/en
Publication of CN101643450A publication Critical patent/CN101643450A/en
Application granted granted Critical
Publication of CN101643450B publication Critical patent/CN101643450B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention discloses a synthesis method for multi substituted 2, 3-dihydro-4(1H)-pyrimidin thionone, belonging to the organic synthesis field. The method comprises the following steps of: (a) reacting end hydrocarbon compound and hydrocarbyl metal compound in ether solvent; reacting temperature being between the freezing point of the solvent and zero DEG C; (b) adding sulphur simple substance to continue the reaction and naturally warming up to the room temperature; (c) adding carbodiimide and rising the reaction temperature to be 60-100 DEG C; (6) postprocessing reaction liquid to obtain multi substituted 2, 3-dihydro-4(1H)-pyrimidin thionone. The method uses the end hydrocarbon compound and the carbodiimide to prepare 2, 3-dihydro-4(1H)-pyrimidin thionone derivative, has higher yield, is scientific and reasonable, has easily obtained raw materials, and has wide application range and high separation yield; and experimental facilities and operation are simple and practicable and convenient for being further developed and applied.

Description

A kind of polysubstituted 2, the synthetic method of 3-dihydro-4 (1H)-pyrimidine thioketone
Technical field
The present invention relates to have multiple substituent 2, the universal synthesis method of 3-dihydro-4 (1H)-pyrimidine thioketone derivative belongs to the organic synthesis field.
Background technology
Have multiple substituently 2,3-dihydro-pyrimidine thioketone derivative is the important synthetic precursor of medicine, is widely used in synthetic uracil medicine, and this compounds is also important organic synthesis molecule simultaneously.At present bibliographical information mostly is polysubstituted 2, the synthetic method of 3-dihydro-2 (1H)-pyrimidine thioketone, and the synthetic method of 2,3-dihydro-4 (1H)-pyrimidine thioketone derivative only has the only a few bibliographical information.Document provides in synthetic method, and the synthetic difficulty of starting raw material is large.The invention provides a kind of method of synthesizing from general industrial chemicals, efficient is high, and cost is low, compared with existing method, has larger application prospect and value.
Summary of the invention
The purpose of this invention is to provide a kind of synthetic have multiple substituent 2, the universal method of 3-dihydro-4 (1H)-pyrimidine thioketone derivative.Technical scheme of the present invention is as follows:
A kind of synthetic polysubstituted 2, the method for 3-dihydro-4 (1H)-pyrimidine thioketone derivative comprises the following steps:
A) the end hydrocarbon compound shown in formula I and alkide (RM) are reacted in ether solvent, temperature of reaction is between the zero pour of described solvent and 0 ℃;
B) add sulphur simple substance to continue reaction, naturally be warming up to room temperature;
C) add the carbodiimide shown in formula II, temperature of reaction is risen to 60-100 ℃;
D) reaction solution obtains polysubstituted 2 shown in formula III, 3-dihydro-4 (1H)-pyrimidine thioketone through aftertreatment.
Its primitive reaction formula is as follows:
Figure G2009100921208D00011
Wherein:
R 1And R 2Can be the same or different, independently of one another expression:
Carbonatoms is 1-12 or more alkyl, such as: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-..., undecyl, dodecyl, tridecyl ..., octadecyl etc., more preferably C1-6 alkyl, more preferably C1-4 alkyl;
Carbonatoms is the cycloalkyl of 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
Carbonatoms is the aryl of 6-12, such as phenyl, xenyl, naphthyl etc.;
Or carbonatoms is the heterocyclic aryl of 2-5, such as thienyl, thiazolyl, pyridyl etc.
Above-mentioned group can be substituted base and replace, and described substituting group can be common C1-4 alkyl or alkoxyl group, C4-6 cycloalkyl, halogen atom (F, Cl, Br, I), cyano group, nitro etc.
Especially, work as R 1Expression is during phenyl, and between its substituting group must be positioned at, position or contraposition, can not be the ortho position, the alkyl that replaces as contraposition, a position, alkoxyl group, halogen atom etc.
R 3And R 4Can be the same or different, independently of one another expression:
Hydrogen;
Carbonatoms is 1-12 or more alkyl, such as: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-..., undecyl, dodecyl, tridecyl ..., octadecyl etc., more preferably C1-6 alkyl, more preferably C1-4 alkyl;
Carbonatoms is the cycloalkyl of 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
Carbonatoms is the aryl of 6-12, such as phenyl, xenyl, naphthyl etc.;
Or carbonatoms is the heterocyclic aryl of 2-5, such as thienyl, thiazolyl, pyridyl etc.
Above-mentioned group can be substituted base and replace, and described substituting group can be common C1-4 alkyl or alkoxyl group, C4-6 cycloalkyl, halogen atom (F, Cl, Br, I), cyano group, nitro etc.
R 3And R 4Also can Cheng Huan, the ring carbon number is 4-6, as shown in embodiment 1 formula III a.
The preferred n-Butyl Lithium of alkide RM used in the present invention or tert-butyl lithium, useful commercial reagent need not special processing.
Ether solvent used in the present invention can be alkyl oxide, aryl oxide or cyclic ethers, can be a kind of ether, can be also the mixture of multiple ether, ether solvent commonly used such as ether, tetrahydrofuran (THF), methyltetrahydrofuran etc.This ether solvent useful commercial reagent is back to mazarine through sodium-benzophenone before using and steams and get final product.
The mol ratio preferable range of various reaction raw materials of the present invention or reagent is as shown in table 1:
The preferred molar ratio of the various reaction raw materials of table 1. or reagent
Raw material or reagent Terminal alkyne compound Alkide Ether solvent S 8 Carbodiimide
Molar equivalent 1-1.2 1-1.2 Arbitrarily 0.125-0.15 1
The ratio of the inventive method opposite end hydrocarbon compound and ether solvent is not particularly limited, as long as can make the reaction solution uniform stirring, the end hydrocarbon compound of preferred 1mmol is dissolved in volume greater than the ether solvent of 2mL.
It is how much slightly different according to different raw materials that the inventive method respectively goes on foot the reaction times, detects to disappear to be as the criterion general 2-3 hour with raw material.
Step c of the present invention can adopt oil bath (for example silicone oil, paraffin wet goods) or other modes to heat, as long as maintain temperature of reaction.
Usually make with the following method reaction product is carried out aftertreatment: add entry or neutrality, weakly alkaline aqueous solution cancellation, water repeatedly extracts with organic solvent, merge organic phase, wash with saturated nacl aqueous solution, filter after adding desiccant dryness in the backward organic phase of separatory, the filtrate concentration process can adopt the methods such as air distillation, underpressure distillation, and is for example concentrated with Rotary Evaporators.
In order to obtain more highly purified product, preferably the product after aftertreatment is carried out purifying, described purge process can be made eluent with the solvent of certain polarity, and the chromatographic column separation gets final product.Selected eluent has different according to the opposed polarity of product.Generally, to select volume ratio be sherwood oil to eluent: methylene dichloride=2: 1 also adds the mixed solvent of 3% triethylamine.The chromatographic column of using silicagel column as commonly used in the laboratory or high performance liquid chromatography etc.
The present invention utilizes end hydrocarbon compound and carbodiimide to prepare 2,3-dihydro-4 (1H)-pyrimidine thioketone derivative, productive rate is higher, and synthetic method is scientific and reasonable, thereby provide one synthetic have multiple substituent 2, the universal method of 3-dihydro-4 (1H)-pyrimidine thioketone derivative.The method raw material is easy to get, and is applied widely, high isolated yield, and experimental installation and operation is simple is convenient to further Application and Development.
Embodiment
Further describe the present invention below in conjunction with embodiment, but the scope that does not limit the present invention in any way.
Embodiment 1---preparation formula IIIa (R 1=Ph, R 2=Cy, R 3+ R 4=Cy) compound:
Figure G2009100921208D00031
Add the 1mmol phenylacetylene in the reaction tubes of the 20mL that the 2ml ether is housed under nitrogen protection, adopt dry ice-propanone to bathe temperature of reaction is constant in-78 ℃, drip the 1mmol n-Butyl Lithium, add afterreaction half an hour, add 0.125mmol S 8, naturally be warming up to 25 ℃, magnetic agitation reaction two hours.Add 1mmolN, N '-dicyclohexylcarbodiimide rises to 80 ℃ of reactions six hours.Add the shrend reaction of going out, water dichloromethane extraction three times, merge organic phase, wash with saturated nacl aqueous solution, add anhydrous magnesium sulfate in the backward organic phase of separatory, dry 30 minutes, normal pressure filters, filtrate is concentrated, and the silicagel column decolouring separates, and uses sherwood oil: methylene dichloride=2: 1 and the mixed solvent that adds 3% (weight percent) triethylamine are as eluent, obtain pyrimidine thioketone derivative 1-cyclohexyl-3-phenyl-4-sulfo--1,5-diaza-spiro [5.5] 10 one-2-alkene 252mg (purity＞98%, yellow solid), isolated yield 74%.The nuclear magnetic data of this compound is as follows: 1HNMR (300MHz, CDCl 3, Me 4Si, 25 ℃): δ=1.32-1.87 (m, 18H, CH 2), 2.26-2.32 (m, 2H, CH 2), 3.24-3.33 (m, 1H, CH), 6.88 (s, 1H, CH), 6.88-6.99 (m, 1H, CH), 7.30-7.34 (m, 3H, CH), 7.47-7.49 (m, 1H, CH), 7.48 (br, 1H, NH); 13C NMR (75MHz, CDCl 3, Me 4Si, 25 ℃): δ=21.12 (2CH 2), 24.44 (1CH 2), 24.88 (1CH 2), 25.86 (2CH 2), 32.58 (2CH 2), 34.69 (2CH 2), 55.57 (1CH), 73.46 (1quat.C), 113.42 (1quat.C), 126.04 (1CH), 127.60 (2CH), 129.67 (2CH), 138.44 (1quat.C), 138.66 (1CH), 185.19 (1quat.C).
Embodiment 2---preparation formula IIIb (R 1=OMe, R 2= iPr, R 3=R 4=Me) compound:
Figure G2009100921208D00041
Add 1mmol 4-methoxyl group-phenylacetylene in the reaction tubes of the 20mL that the 3ml tetrahydrofuran (THF) is housed under nitrogen protection, drip n-Butyl Lithiums at-78 ℃, add afterreaction half an hour, add 0.15mmol S 8, be warming up to 25 ℃ of left and right, magnetic agitation reaction two hours.Add 1mmol N, N '-DIC rises to 100 ℃ of reactions four hours.Add the shrend reaction of going out under zero degree, water dichloromethane extraction three times, merge organic phase, wash with saturated nacl aqueous solution, add anhydrous magnesium sulfate in the backward organic phase of separatory, dry 30 minutes, normal pressure filters, and filtrate is concentrated, and the silicagel column decolouring separates, use sherwood oil: methylene dichloride=2: 1 and the mixed solvent that adds 3% triethylamine are as eluent, obtain straight product 1-sec.-propyl-2,2-dimethyl-5-(4-methoxyl group-phenyl)-2,3-dihydro-4 (1H)-pyrimidine thioketone 0.191g (purity＞98%, yellow solid), isolated yield 66%.The nuclear magnetic data of this compound is as follows: 1H NMR (300MHz, CDCl 3, Me 4Si, 25 ℃): δ=1.30 (d, J=6.9Hz, 6H, CH 3), 1.60 (s, 6H, CH 3), 3.62-3.71 (m, 1H, CH), 3.81 (s, CH 3), 6.78 (s, CH), 6.88 (d, J=8.7Hz, 2H, CH), 7.38 (d, J=8.7Hz, 2H, CH), 7.59 (br, 1H, NH); 13C NMR (75 MHz, CDCl 3, Me 4Si, 25 ℃): δ=23.96 (2CH 3), 25.88 (2CH 3), 47.68 (1CH), 55.21 (1CH 3), 72.29 (1quat.C), 112.96 (1quat.C), 113.20 (1CH), 130.98 (1CH), 131.05 (1quat.C), 137.36 (1CH), 158.12 (1quat.C), 185.99 (1quat.C).
Embodiment 3---preparation formula IIIc (R 1=Pr, R 2= iPr, R 3=R 4=Me) compound:
Figure G2009100921208D00051
With embodiment 2, aftertreatment is identical substantially for synthetic route.This synthetic raw material that sets out is the 1-pentyne of 1.2mmol, obtains straight product 1-sec.-propyl-2,2-dimethyl-5-n-propyl-2,3-dihydro-4 (1H)-pyrimidine thioketone 187mg (purity＞98%, yellow solid), isolated yield 83%.The nuclear magnetic data of this compound is as follows: 1H NMR (300MHz, CDCl 3, Me 4Si, 25 ℃): δ=0.91 (t, J=7.2Hz, 3H, CH 3), 1.27 (d, J=6.6Hz, 6H, CH 3), 1.48-1.58 (m, 2H, CH 2), 1.54 (s, 6H, CH 3), 2.37-2.49 (m, 2H, CH 2), 3.58-3.67 (m, 1H, CH), 6.54 (s, 3H, CH), 8.03 (br, 1H, NH); 13C NMR (75MHz, CDCl 3, Me 4Si, 25 ℃): δ=13.30 (1CH 3), 22.80 (1CH 2), 23.62 (2CH 3), 24.95 (2CH 3), 32.72 (1CH 2), 46.88 (1CH), 71.50 (1quat.C), 110.05 (1quat.C), 135.98 (1CH), 185.65 (1quat.C).
Embodiment 4---preparation formula IIId (R 1=Thiophenyl, R 2= iPr, R 3=R 4=Me) compound:
Figure G2009100921208D00052
With embodiment 2, aftertreatment is identical substantially for synthetic route.This synthetic raw material that sets out is 3-thiophene acetylene, uses the 1.2mmol tert-butyl lithium.Obtain straight product 141mg (purity＞98%, yellow solid), isolated yield 53%.The nuclear magnetic data of this compound is as follows: 1H NMR (300MHz, CDCl 3, Me 4Si, 25 ℃): δ=1.32 (d, J=6.9Hz, 6H, CH 3), 1.60 (s, 6H, CH 3), 3.64-3.73 (m, 1H, CH), 6.91 (s, CH), 7.26 (br, 1H, CH), 7.38-7.40 (m, 2H, CH), 7.52 (br, 1H, NH); 13C NMR (75MHz, CDCl 3, Me 4Si, 25 ℃): δ=24.01 (2CH 3), 25.95 (2CH 3), 47.90 (1CH), 72.22 (1quat.C), 121.06 (1CH), 123.81 (1CH), 129.29 (1CH), 129.32 (1quat.C), 137.70 (1CH), 138.57 (1quat.C), 185.52 (1quat.C).
Embodiment 5---preparation formula IIIe (R 1=Ph, R 2=Ph, R 3=H, R 4=Ph) compound:
Figure G2009100921208D00061
With embodiment 2, aftertreatment is identical substantially for synthetic route.This synthetic carbodiimide that uses is N-phenyl-N-3-thiophene acetylene, and the straight product that obtains at last is 140mg (purity＞98%, yellow solid), isolated yield 53%.

Claims (7)

1.一种多取代2,3-二氢-4(1H)-嘧啶硫酮的合成方法，其特征在于，包括下列步骤：1. a kind of synthetic method of substituted 2,3-dihydro-4 (1H)-pyrimidinethione, is characterized in that, comprises the following steps: a)将式I所示的端烃化合物与烃基金属化合物在醚类溶剂中反应，反应温度在所述溶剂的凝固点和0℃之间；a) reacting the terminal hydrocarbon compound represented by formula I with a metal hydrocarbyl compound in an ether solvent, and the reaction temperature is between the freezing point of the solvent and 0° C.; b)加入硫单质继续反应，自然升温至室温；b) adding sulfur element to continue the reaction, and naturally warming up to room temperature; c)加入式II所示的碳二亚胺，将反应温度升至60-100℃；c) adding carbodiimide represented by formula II, raising the reaction temperature to 60-100°C; d)反应液经后处理得到式III所示的多取代2,3-二氢-4(1H)-嘧啶硫酮，d) the reaction solution is post-treated to obtain the multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione shown in formula III,
Figure FDA00002981018800011
Figure FDA00002981018800011
 其中，R1和R2各自独立地表示取代或非取代的C1-12烷基、C3-6环烷基、C6-12芳基、或C2-12杂环芳基；R3和R4各自独立地表示氢、取代或非取代的C1-12烷基、C6-12芳基、或C2-5杂环芳基，R3和R4可以成C4-6环；所述取代基为C1-4烷基或烷氧基、C4-6环烷基、卤原子、氰基和硝基。Wherein, R 1 and R 2 each independently represent substituted or unsubstituted C 1-12 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, or C 2-12 heterocyclic aryl; R 3 and R 4 each independently represent hydrogen, substituted or unsubstituted C 1-12 alkyl, C 6-12 aryl, or C 2-5 heterocyclic aryl, R 3 and R 4 can form a C 4-6 ring ; The substituent is a C1-4 alkyl or alkoxy group, a C4-6 cycloalkyl group, a halogen atom, a cyano group and a nitro group. 2.如权利要求1所述的合成方法，其特征在于，所述烃基金属化合物是正丁基锂或叔丁基锂。2. synthetic method as claimed in claim 1, is characterized in that, described hydrocarbyl metal compound is n-butyllithium or tert-butyllithium. 3.如权利要求1所述的合成方法，其特征在于，所述醚类溶剂选自：烷基醚、芳醚或环醚或它们的混合物。3. synthetic method as claimed in claim 1, is characterized in that, described ether solvent is selected from: alkyl ether, aryl ether or cyclic ether or their mixture. 4.如权利要求3所述的合成方法，其特征在于，所述醚类溶剂是乙醚、四氢呋喃、甲基四氢呋喃或它们的混合物。4. synthetic method as claimed in claim 3, is characterized in that, described ether solvent is ether, tetrahydrofuran, methyl tetrahydrofuran or their mixture. 5.如权利要求1所述的合成方法，其特征在于，所述端烃化合物，烃基金属化合物，硫单质和碳二亚胺的摩尔当量比为（1-1.2）：（1-1.2）：（0.125-0.15）：1。5. The synthesis method according to claim 1, characterized in that, the molar equivalent ratio of the terminal hydrocarbon compound, the hydrocarbyl metal compound, sulfur element and carbodiimide is (1-1.2): (1-1.2): (0.125-0.15):1. 6.如权利要求1所述的合成方法，其特征在于，所述后处理包括：加入水或中性、弱碱性水溶液淬灭，水相用有机溶剂多次萃取，合并有机相，用饱和氯化钠溶液洗涤，分液后向有机相中加入干燥剂干燥后过滤，浓缩滤液。6. the synthetic method as claimed in claim 1, is characterized in that, described post-treatment comprises: add water or neutral, weakly alkaline aqueous solution to quench, aqueous phase is extracted with organic solvent repeatedly, merges organic phase, with saturated Wash with sodium chloride solution, separate layers, add a desiccant to the organic phase, dry, filter, and concentrate the filtrate. 7.如权利要求1所述的合成方法，其特征在于，通过色谱柱分离纯化产物，洗脱剂是体积比为2:1的石油醚和二氯甲烷混合溶剂，其中加入重量百分比为3%的三乙胺。7. synthetic method as claimed in claim 1, is characterized in that, by chromatographic column separation and purification product, eluent is sherwood oil and methylene dichloride mixed solvent that volume ratio is 2:1, wherein adding weight percent is 3% of triethylamine.
CN 200910092120 2009-09-01 2009-09-01 A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione Expired - Fee Related CN101643450B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 200910092120 CN101643450B (en) 2009-09-01 2009-09-01 A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 200910092120 CN101643450B (en) 2009-09-01 2009-09-01 A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione

Publications (2)

Publication Number Publication Date
CN101643450A CN101643450A (en) 2010-02-10
CN101643450B true CN101643450B (en) 2013-06-26

Family

ID=41655536

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 200910092120 Expired - Fee Related CN101643450B (en) 2009-09-01 2009-09-01 A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione

Country Status (1)

Country Link
CN (1) CN101643450B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103214394B (en) * 2013-04-25 2015-12-09 北京大学 A kind of Alkynyl imine derivative

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
C. Oliver Kappe.Biologically active dihydropyrimidones of the Biginelli-type — a literature survey.《European Journal of Medicinal Chemistry》.2000,第35卷第1043-1052页. *
José Barluenga, et al..Cycloaddition of Unactivated 2-Aza-1,3-dienes with Heterocumulenes: A Convenient Route to the Synthesis of 1,3-Difunctionalized Compounds.《J. CHEM. SOC. PERKIN TRANS. I》.1988,第1739-1744页. *
JoséBarluenga et al..Cycloaddition of Unactivated 2-Aza-1
Mithun Ashok, et al..Convenient one pot synthesis of some novel derivatives of thiazolo[2,3-b]dihydropyrimidinone possessing 4-methylthiophenyl moiety and evaluation of their antibacterial and antifungal activities.《European Journal of Medicinal Chemistry》.2006,第42卷第380-385页. *
MithunAshok et al..Convenient one pot synthesis of some novel derivatives of thiazolo[2
Thomas U. Mayer, et al..Small Molecule Inhibitor of Mitotic Spindle Bipolarity Identified in a Phenotype-Based Screen.《SCIENCE》.1999,第286卷第971-974页. *

Also Published As

Publication number Publication date
CN101643450A (en) 2010-02-10

Similar Documents

Publication Publication Date Title
CN103232426B (en) Choline Chloride catalysis of functional ionic liquid is prepared the method for 1-benzopyran derivatives
CN111205279B (en) Polysubstituted benzodihydrofuran heterocyclic compound and preparation method and application thereof
CN112961079A (en) Method for dehydrating primary amide into nitriles by cobalt catalysis
CN103130719B (en) A kind of polysubstituted imidazoles Calixarene Derivatives and preparation method
CN103351270A (en) Method for catalyzing Knoevenagel condensation reaction by using function ion liquid
CN105688987B (en) A kind of chiral phosphoric acid catalyst and its synthetic method and application
CN101643450B (en) A kind of synthetic method of multi-substituted 2,3-dihydro-4(1H)-pyrimidinethione
CN109535120B (en) Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone
CN106810537B (en) A kind of chiral catalyst suitable for water-oil two-phase system and its preparation and application
CN103910652B (en) Method for aqueous phase synthesis of cyano-substituted styrene compound
CN102786466B (en) Synthetic method of chiral Salan ligand
CN102127032B (en) Method for synthesizing poly-substituted 5-acyl-2-imine thiazoline
CN105153003A (en) Synthetic method of trifluoromethyl seleno-alkyne compound
CN112538058B (en) Preparation method of oxazole-containing cyclic sulfone compound
CN108976106B (en) (E) Synthesis method of (E) -2-methylene-1, 4-butanedione compounds
CN103242378A (en) Ferrocenyl pyrimidine pincer ligand and preparation method thereof
CN102826985B (en) A kind of preparation method of 1-(3,4,5-trihydroxy-) phenyl-1-alkyl ketone
CN103214394B (en) A kind of Alkynyl imine derivative
CN110698373A (en) Preparation method of N- (2- (methylthio) phenyl) acetamide compound and purification method thereof
CN114573431A (en) Green method for preparing alpha, alpha-dibromo-ketone
CN106146233B (en) It is a kind of（Z）The preparation method of -2- alkyl -3- allyl sulfenyl -3- aryl allyl alcohol class compounds
CN105294416A (en) 1,5-dicarbonyl derivative and preparation method thereof
CN103833554B (en) Method for preparing (2E, 2' E) -acrylate ether compound
CN104292245A (en) Optically-pure chiral copper complex and synthetic method
CN105566122A (en) R-type aryne compound containing binaphthyl units with different substituents and synthetic method thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20130626

Termination date: 20200901