CN110981725B - Synthesis method of difluoroolefin - Google Patents

Synthesis method of difluoroolefin Download PDF

Info

Publication number
CN110981725B
CN110981725B CN201910828777.XA CN201910828777A CN110981725B CN 110981725 B CN110981725 B CN 110981725B CN 201910828777 A CN201910828777 A CN 201910828777A CN 110981725 B CN110981725 B CN 110981725B
Authority
CN
China
Prior art keywords
reaction
olefin
reaction tube
difluoroolefin
glove box
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.)
Active
Application number
CN201910828777.XA
Other languages
Chinese (zh)
Other versions
CN110981725A (en
Inventor
陈景超
周永云
樊保敏
孙蔚青
李康葵
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.)
Yunnan Minzu University
Original Assignee
Yunnan Minzu 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 Yunnan Minzu University filed Critical Yunnan Minzu University
Priority to CN201910828777.XA priority Critical patent/CN110981725B/en
Publication of CN110981725A publication Critical patent/CN110981725A/en
Application granted granted Critical
Publication of CN110981725B publication Critical patent/CN110981725B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention belongs to the technical field of organic fluorides, and particularly relates to an efficient method for synthesizing difluoroolefin. The steps are as follows: step 1, taking olefin as a starting material, adding accurately weighed inorganic base into a Schlenk reaction tube with a stirrer in a glove box, plugging a rubber plug, and moving out of the glove box; step 2, absorbing the organic solvent by using an injector, absorbing the olefin and the ethyl difluoroiodoacetate by using a microsyringe, sequentially adding the mixture into a reaction tube, placing the reaction tube in a constant-temperature magnetic stirrer for stirring reaction at room temperature under the irradiation of 30W blue LED visible light, and monitoring the reaction process by adopting TLC and GC-MS; step 3, after the reaction is finished, taking out the reaction tube, removing the volatile solvent from the reaction liquid by using a rotary evaporator under reduced pressure, and purifying the reaction liquid by using an eluant through column chromatography; the reaction formula is as follows:
Figure DDA0002189964700000011
the method greatly reduces the production cost, has remarkable social benefit and economic benefit, has high reaction selectivity, is simple to operate, and is relatively green and environment-friendly.

Description

Synthesis method of difluoroolefin
Technical Field
The invention belongs to the technical field of organic fluorides, and particularly relates to an efficient method for synthesizing difluoroolefin.
Background
Organofluoro compounds are very important in the pharmaceutical and agrochemical industries, and statistically, about 20 to 25% of drug molecules contain fluorine atoms, and about 15 to 20% of new drugs on the market are organofluoro compounds every year. Since the 70 s, China began to research fluorine-containing pesticides, developed a series of fluorine-containing insecticides and herbicides in sequence, and although the success is achieved, the varieties and the quantity of the fluorine-containing pesticides in China still cannot meet the market demands and need to rely on import in large quantity. Thus, research in the field of fluorine chemistry is worth extensive scientific researchers' efforts.
Currently, in view of the outstanding advantages of fluorine-containing groups in adjusting the intrinsic properties of molecular compounds, the search for new fluorine-containing functional groups is strong, and in recent years, difluoroalkyl (CF) groups2R) has attracted considerable attention due to its special chemical properties, and many new difluoroalkylation reagents and new processes have been reported in succession, CF2R can not only change the performance of a molecular compound, but also realize further modification through a functional group with alkyl, so that difluoroalkylation of bioactive molecules becomes an effective means for modifying the bioactivity of the bioactive molecules, and is increasingly paid attention by researchers in novel drug design and pesticide development, and the development and development of an economical and efficient difluoroalkylation method becomes a research hotspot in the field of fluorine chemistry.
The currently reported olefin difluoroalkylation reaction mainly adopts a transition metal (palladium, copper, nickel and the like) catalysis and a photocatalysis method with noble metal photosensitizer addition, and is still not green and economical, so that a more economical and green olefin difluoroalkylation method needs to be developed, and a more simple, green and economical catalytic system is constructed and developed, so that the olefin difluoroalkylation method has a wide application prospect.
Disclosure of Invention
In order to solve the problems, the invention provides a method for synthesizing difluoroolefin.
The specific technical scheme is as follows: a method for synthesizing difluoroolefin, which comprises the following steps:
step 1, taking olefin as a starting material, adding accurately weighed alkali into a Schlenk reaction tube with a stirrer in a glove box, plugging a rubber plug, and moving out of the glove box;
step 2, absorbing the organic solvent by using an injector, absorbing the olefin and the ethyl difluoroiodoacetate by using a microsyringe, sequentially adding the mixture into a reaction tube, placing the reaction tube in a constant-temperature magnetic stirrer for stirring reaction at room temperature under the irradiation of 30Wblue LED visible light, and monitoring the reaction process by adopting TLC and GC-MS;
step 3, after the reaction is finished, taking out the reaction tube, removing the volatile solvent from the reaction liquid by using a rotary evaporator under reduced pressure, and purifying by column chromatography by using ethyl acetate or petroleum ether as an eluent;
the reaction formula is as follows:
Figure BDA0002189964680000021
preferably, the olefin has a molecular structure of:
Figure BDA0002189964680000022
R＝Alkyl，Alkoxy，CF3，CN，X；
Figure BDA0002189964680000023
R＝Alkyl，Alkoxy，CF3，CN，X；
Figure BDA0002189964680000024
R1，R2＝Alkyl，Alkoxy，CF3，CN，X
Figure BDA0002189964680000031
R＝Alkyl,Alkoxy,CF3，CN,X。
preferably, the base in step 1 is an inorganic base or an organic base.
Preferably, the amount ratio of the olefin to the base substance in step 1 is: 1:3-1:1.
Preferably, the inorganic base is: cesium carbonate, potassium carbonate, sodium bicarbonate, preferably cesium carbonate.
Preferably, the organic base is: triethylamine, tetramethylethylenediamine, diisopropylethylamine, 1, 8-diazabicycloundec-7-ene.
Preferably, the olefin in step 1 is monoaryl terminal olefin, diarylene terminal olefin, coumarone and coumarin derivative.
Preferably, the visible light in step 2 is blue light, natural light or sunlight, preferably blue light.
The solvent is any one of acetonitrile, disulfide sulfoxide, N-dimethylformamide and dioxane, wherein the preferable solvent is acetonitrile.
The beneficial effects are that: 1. the invention utilizes a photocatalysis strategy, takes cheap and easily-obtained cesium carbonate as an alkali additive, can realize the high-selectivity difluoroalkylation of olefin without transition metal and photosensitizer, can greatly reduce the production cost, and has remarkable social benefit and economic benefit.
2. The invention has the advantages of mild catalysis conditions, simple catalysis system and high reaction selectivity.
3. The method is simple to operate and relatively green and environment-friendly.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a nuclear magnetic hydrogen spectrum of the product of example 1;
FIG. 2 is a nuclear magnetic hydrogen spectrum of the product of example 2;
FIG. 3 is a nuclear magnetic hydrogen spectrum of the product of example 3;
FIG. 4 is a nuclear magnetic hydrogen spectrum of the product of example 4;
FIG. 5 is a nuclear magnetic hydrogen spectrum of the product of example 5.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
In a glove box, cesium carbonate (130.0mg,0.4mmol) was accurately weighed and loaded into a schlenk reaction tube with a stirrer, the plug was plugged and removed from the glove box, 1mL of acetonitrile was taken out by syringe suction, a microsyringe sequentially sucks styrene (20.8mg,0.2mmol), ethyl difluoroiodoacetate (100.0mg,0.4mmol) and added to the reaction tube, the reaction tube was stirred at room temperature in a constant temperature magnetic stirrer under the irradiation of 30Wblue LED blue light, and the progress of the reaction was monitored by TLC and GC-MS. After the reaction was completed, the reactor was opened and volatile materials were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as an eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give the olefin difluoroalkylation product (29.7mg, 66% yield, Z/E >99: 1).
1H NMR(400MHz,CDCl3)δ7.45(dd,J＝7.6,1.9Hz,2H),7.41–7.30(m,3H),7.16–6.99(m,1H),6.30(dt,J＝16.2,11.4Hz,1H),4.35(q,J＝7.1Hz,2H),1.36(t,J＝7.1Hz,3H)。
The reaction formula is as follows:
Figure BDA0002189964680000051
example 2
In a glove box, cesium carbonate (130.0mg,0.4mmol) was accurately weighed and loaded into a schlenk reaction tube with a stirrer, the plug was plugged and removed from the glove box, 1mL of acetonitrile was taken out by syringe suction, a microsyringe sequentially sucks p-methylstyrene (23.6mg,0.2mmol) and ethyl difluoroiodoacetate (100.0mg,0.4mmol) and added to the reaction tube, the reaction tube was stirred at room temperature under the irradiation of 30W blue LED light and placed in a constant temperature magnetic stirrer, and the progress of the reaction was monitored by TLC and GC-MS, as shown in FIG. 2. After the reaction was completed, the reactor was opened and volatile materials were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as an eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give the olefin difluoroalkylation product (38.3mg, 80% yield, Z/E >99: 1).
1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.1Hz,2H),7.17(d,J＝8.0Hz,2H),7.04(dt,J＝16.2,2.5Hz,1H),6.25(dt,J＝16.2,11.5Hz,1H),4.34(q,J＝7.1Hz,2H),2.35(s,3H),1.35(t,J＝7.1Hz,3H)。
The reaction formula is as follows:
Figure BDA0002189964680000061
example 3
In a glove box, cesium carbonate (130.0mg,0.4mmol) was accurately weighed and loaded into a schlenk reaction tube with a stirrer, the plug was plugged and removed from the glove box, 1mL of acetonitrile was taken out by syringe suction, p-fluorostyrene (24.4mg,0.2mmol) and ethyl difluoroiodoacetate (100.0mg,0.4mmol) were sequentially sucked by a microsyringe and added to the reaction tube, the reaction tube was stirred at room temperature under the irradiation of 30W blue LED light and placed in a constant temperature magnetic stirrer, and the progress of the reaction was monitored by TLC and GC-MS, as shown in FIG. 3. After the reaction was completed, the reactor was opened and volatile materials were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as an eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give the olefin difluoroalkylation product (36.9mg, 76% yield, Z/E >99: 1).
1H NMR(400MHz,CDCl3)δ7.43(dd,J＝8.7,5.4Hz,2H),7.16–6.92(m,3H),6.23(dt,J＝16.2,11.3Hz,1H),4.35(q,J＝7.1Hz,2H),1.37(t,J＝7.1Hz,3H)。
The reaction formula is as follows:
Figure BDA0002189964680000062
example 4
In a glove box, cesium carbonate (130.0mg,0.4mmol) was accurately weighed and loaded into a schlenk reaction tube with a stirrer, the plug was plugged and removed from the glove box, 1mL of acetonitrile was taken by suction from a syringe, 1-stilbene (36.0mg,0.2mmol) and ethyl difluoroiodoacetate (100.0mg,0.4mmol) were sequentially sucked by a microsyringe and added to the reaction tube, the reaction tube was stirred at room temperature under the irradiation of 30W blue LED blue light and placed in a constant temperature magnetic stirrer, and the progress of the reaction was monitored by TLC and GC-MS. After the reaction was completed, the reactor was opened and volatile materials were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as an eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give an olefin difluoroalkylation product (53.4mg, 89% yield).
1H NMR(400MHz,CDCl3)δ7.48–7.10(m,10H),6.27(t,J＝11.7Hz,1H),3.89(q,J＝7.2Hz,2H),1.16(t,J＝7.2Hz,3H)。
The reaction formula is as follows:
Figure BDA0002189964680000071
example 5
In a glove box, cesium carbonate (130.0mg,0.4mmol) was accurately weighed and loaded into a schlenk reaction tube with a stirrer, the plug was plugged and removed from the glove box, 1mL of acetonitrile was taken out by syringe suction, the chroman (23.6mg,0.2mmol), ethyl difluoroiodoacetate (100.0mg,0.4mmol) were sequentially sucked by a microsyringe and added to the reaction tube, the reaction tube was stirred at room temperature under the irradiation of 30W blue LED light and placed in a constant temperature magnetic stirrer, and the progress of the reaction was monitored by TLC and GC-MS. After the reaction was completed, the reactor was opened and volatile materials were removed under reduced pressure using a rotary evaporator, and purified by column chromatography using ethyl acetate and petroleum ether as an eluent. The reaction solvent was concentrated under reduced pressure, followed by column chromatography purification to give an olefin difluoroalkylation product (30.9mg, 68% yield).
1H NMR(400MHz,CDCl3)δ7.73–7.61(m,1H),7.59–7.50(m,1H),7.41(dd,J＝13.7,6.9Hz,1H),7.36–7.27(m,1H),7.16(d,J＝3.6Hz,1H),4.52–4.33(m,2H),1.46–1.32(m,3H)。
The reaction formula is as follows:
Figure BDA0002189964680000081
the above embodiments are merely illustrative of the technical idea and features of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention are included in the scope of the present invention.

Claims (1)

1. A method for synthesizing difluoroolefin is characterized by comprising the following steps:
step 1, taking olefin as a starting material, adding accurately weighed alkali into a Schlenk reaction tube with a stirrer in a glove box, plugging a rubber plug, and moving out of the glove box;
step 2, absorbing the organic solvent by using an injector, absorbing the olefin and the ethyl difluoroiodoacetate by using a microsyringe, sequentially adding the mixture into a reaction tube, placing the reaction tube in a constant-temperature magnetic stirrer for stirring reaction at room temperature under the irradiation of 30Wblue LED visible light, and monitoring the reaction process by adopting TLC and GC-MS;
step 3, after the reaction is finished, taking out the reaction tube, removing the volatile solvent from the reaction liquid by using a rotary evaporator under reduced pressure, and purifying by column chromatography by using ethyl acetate and petroleum ether as an eluent to obtain a difluoroolefin product;
the alkali in the step 1 is cesium carbonate;
the quantity ratio of the olefin to the alkali in the step 1 is as follows: 1:3-1: 1;
the olefin is: p-methylstyrene, p-fluorostyrene or 1, 1-stilbene;
the difluoroolefin product is
Figure FDA0003511045010000011
Figure FDA0003511045010000012
Figure FDA0003511045010000021
CN201910828777.XA 2019-09-03 2019-09-03 Synthesis method of difluoroolefin Active CN110981725B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910828777.XA CN110981725B (en) 2019-09-03 2019-09-03 Synthesis method of difluoroolefin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910828777.XA CN110981725B (en) 2019-09-03 2019-09-03 Synthesis method of difluoroolefin

Publications (2)

Publication Number Publication Date
CN110981725A CN110981725A (en) 2020-04-10
CN110981725B true CN110981725B (en) 2022-04-15

Family

ID=70081678

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910828777.XA Active CN110981725B (en) 2019-09-03 2019-09-03 Synthesis method of difluoroolefin

Country Status (1)

Country Link
CN (1) CN110981725B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108503546A (en) * 2018-05-16 2018-09-07 浙江师范大学 A kind of preparation method of β-fluoroalkyl alkynes
CN110156550A (en) * 2019-06-17 2019-08-23 遵义医科大学 A method of fluoroalkylation is carried out using phenol and its derivatives for photochemical catalyst
CN110172022A (en) * 2019-06-17 2019-08-27 遵义医科大学 A method of fluoroalkyl is carried out using organic phosphorus compound catalyzed alkene

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108503546A (en) * 2018-05-16 2018-09-07 浙江师范大学 A kind of preparation method of β-fluoroalkyl alkynes
CN110156550A (en) * 2019-06-17 2019-08-23 遵义医科大学 A method of fluoroalkylation is carried out using phenol and its derivatives for photochemical catalyst
CN110172022A (en) * 2019-06-17 2019-08-27 遵义医科大学 A method of fluoroalkyl is carried out using organic phosphorus compound catalyzed alkene

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Kangkui Li等.Blue Light Induced Di fluoroalkylation of Alkynes and Alkenes.《Org. Lett. 》.2019,第21卷 *

Also Published As

Publication number Publication date
CN110981725A (en) 2020-04-10

Similar Documents

Publication Publication Date Title
CN108069934B (en) Method for preparing polyaromatic substituted naphthalene derivative by reaction of biphenyl type arone and tolane catalyzed by ruthenium
CN109942364B (en) Olefin synthesis method using water as hydrogen source
CN110551031A (en) method for water-phase catalysis Henry asymmetric addition reaction based on polyion liquid type chiral copper amino acid catalyst
CN113788756B (en) Method for synthesizing optically pure allyl alcohol compound through diacid catalysis in green mode
CN108164475A (en) A kind of method for the line style heterocyclic base ketone for catalyzing and synthesizing difluoromethyl substitution
CN108863840A (en) The fluorinated derivatives and preparation method thereof of azo-based benzene
CN110981725B (en) Synthesis method of difluoroolefin
CN112047839B (en) 1-iodine-3-perfluoroalkyl alkene compound and preparation method thereof
CN106986886B (en) A kind of preparation method of the fluoro- 3- Trifluoromethoxyphen-l pinacol borate of 4-
CN110066246B (en) Method for preparing isoquinoline-1-ketone derivative
CN111072605B (en) Preparation method of fluoroalkyl-substituted benzofuran derivative or indole derivative
CN107382910B (en) Difluoromethyl aldehyde hydrazone compound and preparation method thereof
CN110551024B (en) Preparation method of difluoro iodo olefin
CN115010753A (en) Method for preparing phosphorylated gem-difluorodiene compound in aqueous phase
CN107973715B (en) Preparation method of polysubstituted remote allyl ketone derivative
CN112409345A (en) Preparation method of novel dihydropyronyl coumarin compound
CN108299369B (en) Coumarin-4-sulfonic acid ester derivative and preparation method thereof
CN110950739A (en) Method for directly fluorinating ortho-position of phenol compound
CN101602670A (en) A kind of 5-chloro-1-oxo-2, the preparation method of 3-dihydro indenes-2-carboxylate methyl ester
CN110668940A (en) Synthesis method of alpha, beta-unsaturated carboxylic ester derivative by visible light catalysis
CN112441997B (en) Method for synthesizing alpha- (2-tetrahydrofuryl) -acetophenone compound
CN110194760B (en) Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones
CN114213370B (en) Method for synthesizing alkylated electron-rich heterocyclic aromatic hydrocarbon by photo-induced NHPI ester decarboxylation coupling
CN115850076A (en) Method for introducing difluoromethylene into allyl ester compound aromatic ring
CN107739322B (en) Synthetic method of sulfonamide compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant