CN102219638B - Fluorination method of vinyl carboxylic acid - Google Patents

Fluorination method of vinyl carboxylic acid Download PDF

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CN102219638B
CN102219638B CN201010150373.9A CN201010150373A CN102219638B CN 102219638 B CN102219638 B CN 102219638B CN 201010150373 A CN201010150373 A CN 201010150373A CN 102219638 B CN102219638 B CN 102219638B
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CN102219638A (en
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胡金波
何正标
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention relates to a decarboxylation and fluorination method of vinyl carboxylic acid. In the method, in an aqueous or polar organic solvent or a mixed solvent of aqueous and polar organic solvents, vinyl carboxylic acid, an additive and an electrophilic fluorinating reagent are reacted at room temperature-reflux temperature so as to synthesize monofluoro olefin, allyl fluoride, difluoro alkyl substituted alcohol, mono-difluoro alkyl substituted alcohol, monofluoro alkyl substituted epoxide, beta-monofluoro/difluoro substituted cyclic lactone or beta-monofluoro substituted unsaturated cyclic lactone compounds. The structural formula of vinyl carboxylic acid is shown in the specification. According to the method in the invention, raw materials are available, reaction is simple and convenient, and the method can be used for preparing compounds which are difficult to prepare by using a common method.

Description

A kind of fluorination process of thiazolinyl carboxylic acid
Technical field
The present invention relates to the fluorination process of thiazolinyl carboxylic acid, further say a kind of electrophilic fluorination reaction of thiazolinyl carboxylic acid, and utilize these to react to single fluoroolefin, allyl group fluorochemical, the alcohol that fluoroalkyl replaces, the alcohol that two single fluoroalkyls replace, the epoxy compounds that single fluoroalkyl replaces, the unsaturated cyclic lactone compounds that the cyclic lactone that β-mono-fluorine replaces, two fluorine replaces and β-mono-fluorine replaces synthetic.
Background technology
Drugs Containing Fluorine and agricultural chemicals are all generally to contain single fluorine atom or lack fluorin radical as the compound of difluoromethyl and trifluoromethyl etc.A large amount of facts shows after fluorine atom or fluoro-containing group introducing molecule, can to change the physiologically active of molecule.This is mainly because the peculiar property of fluorine atom determines, such as difluoromethyl (CF 2h) with methylol (CH 2oH) body and the isopolarity such as have, difluoromethyl can also be served as lipophilic hydrogen bond donor simultaneously, thereby difluoromethyl compound heavily has potential extensive use in life science, medicinal design and novel material exploitation.Therefore, optionally fluoridize the research of reacting with fluoroalkylation at medicine, in the fields such as agricultural chemicals and material, more and more come into one's own.
The decarboxylation fluoridation of saturated carboxylic acid has report ((a) Patrick, T.B., Johri, K, K., White, D.H., J.Org.Chem.1983,48,4158 very early; (b) Patrick, T.B., Johri, K, K., White, D.H., Bertrand, W.S., Mokhtar, R., Kilbourn, M.R., Welch, M.J., Can.J.Chem.1986,64,138), for the decarboxylation bromination of unsaturated carboxylic acid, chlorination also realizes (Naskar, D., Roy, S., Tetrahedron 2000,56,1369), but but never have people's report for the electrophilic fluorination decarboxylic reaction of unsaturated carboxylic acid.The present invention has realized the electrophilic fluorination decarboxylic reaction of polytype unsaturated carboxylic acid.
Summary of the invention
The object of this invention is to provide a kind of fluorination process of thiazolinyl carboxylic acid, relate to a kind of electrophilic fluorination decarboxylic reaction of thiazolinyl carboxylic acid, a kind of synthetic single fluoroolefin is provided, allyl group fluorochemical, the alcohol that fluoroalkyl replaces, the alcohol that two single fluoroalkyls replace, the epoxy compounds that single fluoroalkyl replaces, β-mono-fluorine replaces, the method for the cyclic lactone that two fluorine replace and β-unsaturated cyclic lactone compounds that mono-fluorine replaces.
Method of the present invention is in water, polar organic solvent or their mixed solvent; Thiazolinyl carboxylic acid, additive and electrophilic fluorination reagent react 2～70 hours under room temperature～reflux temperature;
The mol ratio of described thiazolinyl carboxylic acid, additive and electrophilic fluorination reagent is 1: 1.2～5: 1.
The thiazolinyl carboxylic acid the present invention relates to has following structure:
Wherein, n=0 or 1; R 1for alkyl, phenyl, the R of hydrogen, C1～C9 11alkoxyl group or the carboxyl of the phenyl, the furan nucleus that replace, pyridyl, C1～C9; R 2for alkyl, phenyl, the R of hydrogen, C1～C9 11alkoxyl group or the carboxyl of the phenyl, the furan nucleus that replace, pyridyl, C1～C9; R 3for alkyl, phenyl, the R of hydrogen, C1～C9 10the phenyl, furan nucleus, pyridyl, the alkoxyl group of C1～C9, carboxyl, halogen, cyano group, aldehyde radical, the ester group or trimethyl silicon based that replace; R 11for alkyl, phenyl, halogen, the nitro of C1～C9;
Method of the present invention, i.e. the electrophilic fluorination of thiazolinyl carboxylic acid reaction can represent with typical reaction formula below:
Wherein n=0 or 1; R 1, R 2, R 3as previously mentioned; R 4for R 1, R 2, R 3, H, F or CFR 1r 2; R 5for R 1, R 2, R 3, H, F or CFR 1r 2; R 6for R 1, R 2, R 3, H, F or CFR 1r 2; R 8for R 1, R 2, R 3, CF 2r 3, CH 2f or CFR 1r 2; R 9for R 1, R 2, R 3, CF 2r 3, CH 2f or CFR 1r 2; R 10for R 1, R 2, R 3, CF 2r 3, CH 2f or CFR 1r 2; The solvent (Solvent) of reaction is the mixed solvent of water, polar organic solvent or water and polar organic solvent; The additive (Additive) of reaction is nickel acetate, sodium-acetate lithium or sodium carbonate; Electrophilic fluorination reagent (" F +") be F 2, XeF 2, " O-F " reagent or " N-F " reagent.Described " O-F " reagent is FClO 3, CF 3oF or CH 3cO 2f; Described " N-F " reagent is Selectfluor tM, NFTH or NFSI etc.: described polar organic solvent is tetracol phenixin (CCl 4), acetonitrile (CH 3or trifluoracetic acid (CF CN) 3cOOH).
The thiazolinyl carboxylic acid the present invention relates to, again can be concrete according to its constitutional features be divided into following six types:
Wherein R 1, R 2, R 3as previously mentioned.
Described thiazolinyl carboxylic acid can also further describe the compound for having following structural formula:
In the inventive method, can also according to the type reaction of above-mentioned dissimilar thiazolinyl carboxylic acid more further refinement be described below:
The electrophilic fluorination reaction of the 1st type thiazolinyl carboxylic acid (α, beta-unsaturated carboxylic acid) can represent with typical reaction formula below:
(reaction formula 1):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: water, and tetracol phenixin and trifluoroacetic mixed solvent, its volume ratio is 2: 2: 0.2～2; Additive is nickel acetate or Lithium Acetate etc.); The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 1.2～1.5: 1, and temperature of reaction is 50～100 DEG C. the reaction times is 2～70 hours.
In the present invention, the electrophilic fluorination of the 1st type thiazolinyl carboxylic acid (α, beta-unsaturated carboxylic acid) reaction can represent with typical reaction formula below:
(reaction formula 2):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: water and trifluoroacetic mixed solvent, and its volume ratio is 5: 1～2.5, additive is nickel acetate or Lithium Acetate.The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～5: 1, and temperature of reaction is 50～100 DEG C. the reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 2nd type thiazolinyl carboxylic acid (beta, gamma-unsaturated carboxylic acid) in the present invention can represent with typical reaction formula below:
(reaction formula 3):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: the mixed solvent of water and tetracol phenixin, and its volume ratio is 3: 2, additive is nickel acetate or sodium carbonate.The ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 3: 4: 3, and temperature of reaction is room temperature. the reaction times is 2～70 hours.
The electrophilic fluorination of the 2nd type thiazolinyl carboxylic acid (beta, gamma-unsaturated carboxylic acid) in the present invention also reacts and can represent with typical reaction formula below:
(reaction formula 4):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: the mixed solvent of water and acetonitrile, and the volume ratio of water and acetonitrile is 3: 2, and additive is sodium carbonate or calcium carbonate, and the ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 3: 1, and temperature of reaction is 50～100 DEG C.Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 2nd type thiazolinyl carboxylic acid (beta, gamma-unsaturated carboxylic acid) in the present invention can represent with typical reaction formula below:
(reaction formula 5):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: the mixed solvent of water and acetonitrile, and the volume ratio of water and acetonitrile is 3: 2, and the mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 3: 1, and temperature of reaction is room temperature.Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 3rd type thiazolinyl carboxylic acid (β-carboxyl-beta, gamma-unsaturated carboxylic acid) carboxylic acid in the present invention can represent with typical reaction formula below:
(reaction formula 6):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: water, and tetracol phenixin and trifluoroacetic mixed solvent, its volume ratio is 3: 2: 0.2～1; Additive is nickel acetate or Lithium Acetate; Temperature of reaction is reflux temperature; Reaction times is 2～70 hours; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～5: 2.
The electrophilic fluorination reaction of the 3rd type thiazolinyl carboxylic acid (β-carboxyl-beta, gamma-unsaturated carboxylic acid) carboxylic acid in the present invention can also represent with typical reaction formula below:
(reaction formula 7):
Wherein R 1, R 2, R 3as previously mentioned.The solvent of reaction is: water, and additive is nickel acetate or Lithium Acetate; Temperature of reaction is reflux temperature; Reaction times is 2～70 hours; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～5: 2.
The electrophilic fluorination reaction of the 4th type thiazolinyl carboxylic acid (γ-carboxyl-α, beta-unsaturated carboxylic acid) carboxylic acid in the present invention in the present invention can represent with typical reaction formula below:
(reaction formula 8):
Wherein R 1as previously mentioned.The solvent of reaction is: the mixed solvent of water and tetracol phenixin, and its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～3: 1; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 4th type thiazolinyl carboxylic acid (γ-carboxyl-α, beta-unsaturated carboxylic acid) carboxylic acid in the present invention in the present invention can also represent with typical reaction formula below:
(reaction formula 9):
Wherein R 1as previously mentioned.Reaction solvent be: water and acetonitrile mixed solvent, its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～3: 1, and temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 4th type thiazolinyl carboxylic acid (γ-carboxyl-α, beta-unsaturated carboxylic acid) carboxylic acid in the present invention in the present invention can also represent with typical reaction formula below:
(reaction formula 10):
Wherein R 1as previously mentioned.Reaction solvent be: water and acetonitrile mixed solvent, its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 3～5: 1; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 4th type thiazolinyl carboxylic acid (γ-carboxyl-α, beta-unsaturated carboxylic acid) carboxylic acid in the present invention in the present invention can also represent with typical reaction formula below:
(reaction formula 11):
Wherein R 1as previously mentioned.Reaction solvent be: water and acetonitrile mixed solvent, its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 3～5: 2; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 5th type thiazolinyl carboxylic acid (α-carboxyl-beta, gamma-unsaturated carboxylic acid) in the present invention can represent with typical reaction formula below:
(reaction formula 12):
Wherein R 1as previously mentioned.Reaction solvent be: water and acetonitrile mixed solvent, its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 3～5: 1; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 6th type thiazolinyl carboxylic acid (α-carboxyl-α, beta-unsaturated carboxylic acid) in the present invention can represent with typical reaction formula below:
(reaction formula 13):
Wherein R 1, R 2as previously mentioned.The solvent of reaction is: the mixed solvent of water and tetracol phenixin, and its volume ratio is 3: 2; Additive is nickel acetate or Lithium Acetate; The mol ratio of thiazolinyl carboxylic acid, Selectfluor and additive is 1: 2～3: 1; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
The electrophilic fluorination reaction of the 6th type thiazolinyl carboxylic acid (α-carboxyl-α, beta-unsaturated carboxylic acid) in the present invention can also represent with typical reaction formula below:
(reaction formula 14):
Wherein R 1, R 2as previously mentioned.Reaction solvent be: water and acetonitrile mixed solvent, its volume ratio is 3: 2; Additive is nickel acetate or sodium carbonate; The mol ratio of carboxylic acid, Selectfluor and additive is 1: 3～5: 1; Temperature of reaction is 50～100 DEG C; Reaction times is 2～70 hours.
In a word, first, from the source of raw material, there is a large amount of thiazolinyl carboxylic acids in nature, and its synthetic preparation is also than being easier to simultaneously, and in addition, fluorination reagent is also business-like, can directly buy and obtain, and therefore the acquisition of raw material ratio is easier to.The present invention is simultaneously also the decarboxylation of fluoridizing that has realized first thiazolinyl carboxylic acid, and can utilize these to react and synthesize a series of compounds that utilize other method to be relatively difficult to preparation of system.The structure that is finally thiazolinyl carboxylic acid can change according to concrete needs (the thiazolinyl carboxylic acid of six types above), thereby prepares the target compound of special construction.
Embodiment
Utilize following embodiment will contribute to understand the present invention, but do not limit content of the present invention.
Embodiment 1
In the reaction tubes of being furnished with built-in reflux condensing tube, add successively 3,3-diphenylacrylate (112mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), two hydration nickel acetates (124mg, 0.5mmol), 2mL tetracol phenixin, 3mL water, 0.5mL trifluoracetic acid, stirs reflux 40 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 79mg colourless liquid, productive rate 80%.
Embodiment 2
Reaction tubes the inside at the 20mL that is furnished with built-in reflux condensing tube adds 3,3-diphenylacrylate (112mg, 0.5mmol) successively, Selectfluor (532mg, 1.5mmol), 5mL water, 1mL trifluoracetic acid, stirs reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 104mg colourless liquid, productive rate 89%.
Embodiment 3
Reaction tubes the inside at the 20mL that is furnished with built-in reflux condensing tube adds 3-(4-nitrophenyl) vinylformic acid (104mg, 0.5mmol), Selectfluor (532mg successively, 1.5mmol), 5mL water, 1mL trifluoracetic acid, stir reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 53mg colourless liquid, productive rate 43%.
Embodiment 4
In the reaction tubes of being furnished with built-in reflux condensing tube, add successively 1-methyl-3-(4-bromophenyl)-3-phenylacrylic acid (159mg, 0.5mmol), Selectfluor (532mg, 1.5mmol), two hydration nickel acetates (124mg, 0.5mmol), 5mL water, 0.5mL trifluoracetic acid, stirs reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 135mg colorless solid, productive rate 83%.
Embodiment 5
In the reaction tubes of being furnished with built-in reflux condensing tube, add successively 1,3,3-triphenyl vinylformic acid (150mg, 0.5mmol), Selectfluor (532mg, 1.5mmol), two hydration nickel acetate (124mg, 0.5mmol), 3mL water, 2mL acetonitrile, 0.5mL trifluoracetic acid, stir reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 115mg white solid, productive rate 73%.
Embodiment 6
In the reaction tubes of being furnished with built-in reflux condensing tube, add successively 1-normal-butyl-3-(4-fluorophenyl)-3-phenylacrylic acid (149mg, 0.5mmol), Selectfluor (532mg, 1.5mmol), two hydration nickel acetates (124mg, 0.5mmol), 5mL water, 0.5mL trifluoracetic acid, stirs reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 120mg colorless solid, productive rate 78%.
Embodiment 7
In the reaction tubes of being furnished with built-in reflux condensing tube, add successively 1-chloro-3,3-diphenylacrylate (129mg, 0.5mmol), Selectfluor (532mg, 1.5mmol), trifluoracetic acid triethylamine salt (108mg, 0.5mmol), 4mL water, 1mL trifluoracetic acid, stir reflux 60 hours.Cool to room temperature, is first neutralized to weakly alkaline with saturated sodium bicarbonate aqueous solution, then uses dichloromethane extraction, and organic layer concentrated post, obtains 93mg white solid, productive rate 69%.
Embodiment 8
In reaction tubes, add successively 3-(4-aminomethyl phenyl)-3-butenoic acid (88mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), sodium carbonate (53mg, 0.5mmol), 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours.With carbon tetrachloride extraction, concentrated, cross post, obtain 67mg colourless liquid, productive rate 89
Embodiment 9
In reaction tubes, add successively thiazolinyl carboxylic acid (94mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), sodium carbonate (53mg, 0.5mmol), 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours.With carbon tetrachloride extraction, concentrated, cross post, obtain 80mg colourless liquid, productive rate 99%.
Embodiment 10
In reaction tubes, add successively thiazolinyl carboxylic acid (103mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), sodium carbonate (53mg, 0.5mmol), 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours.With carbon tetrachloride extraction, concentrated, cross post, obtain 90mg colourless liquid, productive rate 99%.
Embodiment 11
In reaction tubes, add successively 3-(4-methyl-phenyl)-3-butenoic acid (88mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), sodium carbonate (53mg, 0.5mmol), 3mL water, 2mL acetonitrile, stirring at room temperature 36 hours.With two rate methane extractions, concentrated, cross post, obtain 59mg colourless liquid, productive rate 63%.
Embodiment 12
In reaction tubes, add successively 3-(4-methyl-phenyl)-3-butenoic acid (88mg, 0.5mmol), Selectfluor (213mg, 0.6mmol), 3mL water, 2mL acetonitrile, stirring at room temperature 24 hours.With dichloromethane extraction, concentrated, cross post, obtain 53mg colourless liquid, productive rate 64%.
Embodiment 13
In reaction tubes, add successively 4,4-phenylbenzene-3-carboxyl-3-butenoic acid (141mg, 0.5mmol), Selectfluor (531mg, 1.5mmol), two hydration Lithium Acetates (55mg, 0.5mmol), 2mL water, 2mL tetracol phenixin, reflux 60 hours.Stopped reaction, cool to room temperature, first with saturated sodium bicarbonate aqueous solution neutralization, with dichloromethane extraction, concentrated, cross post, obtain 114mg colorless solid, productive rate 83%.
Embodiment 14
In reaction tubes, add successively 4,4-phenylbenzene-3-carboxyl-3-butenoic acid (141mg, 0.5mmol), Selectfluor (531mg, 1.5mmol), two hydration Lithium Acetate (55mg, 0.5mmol), 5mL water, reflux 60 hours.Stopped reaction, cool to room temperature, first with saturated sodium bicarbonate aqueous solution neutralization, with dichloromethane extraction, concentrated, cross post, obtain 78mg light yellow liquid, productive rate 61%.
Embodiment 15
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid (117mg, 0.5mmol), Selectfluor (531mg, 1.5mmol), sodium carbonate (106mg, 1.5mmol), 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours.Stopped reaction, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 63mg light yellow liquid, productive rate 70%.
Embodiment 16
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid (117mg, 0.5mmol), Selectfluor (531mg, 1.5mmol), sodium carbonate (106mg, 1.5mmol), 3mL water, 2mL acetonitrile, stirring at room temperature 36 hours.Stopped reaction, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 59mg light yellow liquid, productive rate 65%.
Embodiment 17
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid (117mg, 0.5mmol), Selectfluor (708mg, 2.0mmol), sodium carbonate (106mg, 1.5mmol), 3mL water, 2mL acetonitrile, reflux 36 hours.Stopped reaction, is cooled to room temperature and directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 74mg light yellow liquid, productive rate 75%.
Embodiment 18
In reaction tubes, add successively 3,3-phenylbenzene-2-carboxy acrylic (134mg, 0.5mmol), Selectfluor (708mg, 2.0mmol), sodium carbonate (106mg, 1.5mmol), 3mL water, 2mL tetracol phenixin, reflux 36 hours.Stopped reaction, is cooled to room temperature and directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 76mg light yellow liquid, productive rate 75%.
Embodiment 19
In reaction tubes, add successively 3,3-phenylbenzene-2-carboxy acrylic (134mg, 0.5mmol), Selectfluor (708mg, 2.0mmol), sodium carbonate (106mg, 1.5mmol), 3mL water, 2mL acetonitrile, reflux 36 hours.Stopped reaction, is cooled to room temperature and directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 76mg light yellow liquid, productive rate 60%.

Claims (5)

1. a decarboxylation fluorination process for thiazolinyl carboxylic acid, is characterized in that in water, tetracol phenixin, polar organic solvent or their mixed solvent; Thiazolinyl carboxylic acid, additive and electrophilic fluorination reagent react 2～70 hours under room temperature～reflux temperature;
The mol ratio of described thiazolinyl carboxylic acid, additive and electrophilic fluorination reagent is 1: 1.2～5: 1;
Described thiazolinyl carboxylic acid has following structure:
Wherein, n=0 or 1; R 1for alkyl, phenyl, the R of hydrogen, C1～C9 11alkoxyl group or the carboxyl of the phenyl, the furan nucleus that replace, pyridyl, C1～C9; R 2for alkoxyl group or the carboxyl of the alkyl of hydrogen, C1～C9, phenyl, furan nucleus, pyridyl, C1～C9; R 3for alkyl, phenyl, furan nucleus, pyridyl, the alkoxyl group of C1～C9, carboxyl, halogen, cyano group, aldehyde radical, the ester group or trimethyl silicon based of hydrogen, C1～C9; R 11for alkyl, phenyl, halogen, the nitro of C1～C9;
Described additive is nickel acetate, Lithium Acetate or sodium carbonate;
Described electrophilic fluorination reagent is F 2, XeF 2, " O-F " reagent or " N-F " reagent; Described " O-F " reagent is FClO 3, CF 3oF or CH 3cO 2f; Described " N-F " reagent is Selectfluor, NFTH or NFSI;
Wherein Selectfluor, NFTH and NFSI are as follows:
2. the decarboxylation fluorination process of thiazolinyl carboxylic acid as claimed in claim 1, is characterized in that described thiazolinyl carboxylic acid has
Following structural formula:
Wherein R 1, R 2and R 3as claimed in claim 1.
3. the decarboxylation fluorination process of thiazolinyl carboxylic acid as claimed in claim 1, is characterized in that described thiazolinyl carboxylic acid has following structural formula:
4. the decarboxylation fluorination process of thiazolinyl carboxylic acid as claimed in claim 1, is characterized in that described polar organic solvent is acetonitrile or trifluoracetic acid.
5. a decarboxylation fluorination process for thiazolinyl carboxylic acid, is characterized in that being obtained respectively by following seven kinds of methods: (1),
In reaction tubes, add successively 3-(4-the aminomethyl phenyl)-3-butenoic acid 0.5mmol described in reaction formula, Selectfluor0.6mmol, sodium carbonate 0.5mmol, 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours; With carbon tetrachloride extraction, concentrated, cross post, obtain 67mg colourless liquid, productive rate 89%;
(2)，
In reaction tubes, add successively the thiazolinyl carboxylic acid 0.5mmol described in reaction formula, 0.6mmol Selectfluor, sodium carbonate 0.5mmol, 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours; With carbon tetrachloride extraction, concentrated, cross post, obtain 80mg colourless liquid, productive rate 99%;
(3)，
In reaction tubes, add successively the thiazolinyl carboxylic acid described in 0.5mmol reaction formula, 0.5mmol Selectfluor, 0.5mmol sodium carbonate, 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours; With carbon tetrachloride extraction, concentrated, cross post, obtain 90mg colourless liquid, productive rate 99%;
(4)，
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid 0.5mmol, Selectfluor1.5mmol, sodium carbonate 1.5mmol, 3mL water, 2mL tetracol phenixin, stirring at room temperature 36 hours; Stopped reaction, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 63mg light yellow liquid, productive rate 70%;
(5)，
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid 0.5mmol, Selectfluor1.5mmol, sodium carbonate 1.5mmol, 3mL water, 2mL acetonitrile, stirring at room temperature 36 hours; Stopped reaction, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 59mg light yellow liquid, productive rate 65%;
(6)，
In reaction tubes, add successively 1-methyl-3-carboxyl-indoles-2-acetic acid 0.5mmol, Selectfluor2.0mmol, sodium carbonate 1.5mmol, 3mL water, 2mL acetonitrile, reflux 36 hours; Stopped reaction, is cooled to room temperature, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 74mg light yellow liquid, productive rate 75%;
In reaction tubes, add successively 3,3-phenylbenzene-2-carboxy acrylic 0.5mmol, Selectfluor2.0mmol, sodium carbonate 1.5mmol, 3mL water, 2mL tetracol phenixin, reflux 36 hours; Stopped reaction, is cooled to room temperature, directly uses dichloromethane extraction, with anhydrous magnesium sulfate drying, filters, concentrated, crosses post, obtains 76mg light yellow liquid, productive rate 75%;
Above-mentioned Selectfluor is with described in claim 1.
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