CN108299384A - Trifluoromethylthio transfering reagent compound and its synthetic method - Google Patents
Trifluoromethylthio transfering reagent compound and its synthetic method Download PDFInfo
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- CN108299384A CN108299384A CN201810158577.3A CN201810158577A CN108299384A CN 108299384 A CN108299384 A CN 108299384A CN 201810158577 A CN201810158577 A CN 201810158577A CN 108299384 A CN108299384 A CN 108299384A
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- trifluoromethylthio
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- transfering reagent
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Abstract
The present invention relates to a kind of trifluoromethylthio transfering reagent compound and its synthetic methods; 1 (trifluoromethylthio) nitrogen acetyl group of transfering reagent, 1, the 2 benzenesulfonyl amine 3 (1 of specifically a kind of novel functional group containing trifluoromethylthio based on organic trivalent iodine compoundH) ketone and its synthetic method.The structure of the trifluoromethylthio transfering reagent compound is as follows, has a kind of novelNAcetyl basic ring iodoxy amine skeleton.The reagent has synthetic method efficient, and raw material is easy to get, and operation is easy, product yield, many advantages, such as purity is high.The trifluoromethylthio transfering reagent compound is suitable for commercial synthesis.
Description
Technical field
It is specifically a kind of novel to be based on the present invention relates to a kind of trifluoromethylthio transfering reagent compound and its synthetic method
Transfering reagent 1- (trifluoromethylthio)-nitrogen of the functional group containing trifluoromethylthio of organic trivalent iodine compound-acetyl group -1,2- benzene
Iodoxy amine -3 (1H) -one synthetic method.
Background technology
Trifluoromethylthio has stronger electron-withdrawing ability, can be effectively reduced the cloud density of compound, to
Carry high molecular metabolic stability；And it possesses highest Hansch coefficients (π in common fluorine-containing functional groupx=
1.44) it, is introduced into molecule and can effectively improve the fat-soluble of molecule, enhance the penetrability to cell membrane.Due to trifluoro
Methyl mercapto possesses the above unique property so that it is obtained for extensively in fields such as medicine, pesticide, material and fluorine-containing daily necessities
General application.Therefore, how trifluoromethylthio functional group is effectively introduced into molecule also just becomes current organic fluorine chemistry
One of the research hotspot on boundary.
In recent decades, the method that trifluoromethylthio is much introduced into molecule has been developed in chemists.Especially
It has been since 2008, a series of electrophilic trifluoromethylthio reagent is developed and applied.Such as spread out based on phenyl amines
The Billard reagents of biology（J. Org. Chem. 2008, 73, 9362）, the Shibata reagents based on high price iodonium ylides （J. Am. Chem. Soc. 2013, 135, 8782）, the fluoroform of its imperial seminar's exploitation of Shanghai Institute of Organic Chemistry Lv Long and Shen Base sulfenic acids esters reagent（Angew. Chem. Int. Ed. 2013, 52, 3457）, N- trifluoromethylthio saccharin reagents （Angew. Chem. Int. Ed. 2014, 53, 9316）,NTrifluoromethylthio dibenzenesulfonimide reagent（J. Org. Chem. 2016, 81, 7486）Deng.With trifluoromethylthio chlorine traditional before（CF3SCl）With it is double（Trifluoromethyl）Curing
Object (CF3SSCF3) etc. reagents compare, the side of trifluoromethylthio is introduced directly into molecule using electrophilic trifluoromethylthio reagent
Method have it is easy to use, many advantages, such as stability and high efficiency, substrate spectrum is wide, thus electrophilic trifluoromethylthio reagent increasingly by
To the favor of people.
The organic hypervalent iodine reagent of first case has been synthesized from Germanization scholar Willgerodt in 1886 --- dichloro iodoso
Benzene（J. Prakt, Chem.1886, 33, 156）, over more than 100 years, with flourishing for organic high price means of iodine chemical, and have
Many organic hypervalent iodine reagents are synthesized, report in succession.Why organic hypervalent iodine reagent can obtain the extensive pass of chemists
Note, traces it to its cause and is predominantly due to the following aspects：（1）Organic hypervalent iodine reagent contains abundant reactivity, some of
Reactivity it is similar to transient metal complex, and many natural products it is fully synthetic in played an important role；（2）Have
Machine hypervalent iodine reagent is a kind of environmentally friendly compound.Organic hypervalent iodine reagent has and Hg (II), Tl (III), Pb (IV)
The similar chemical property of equal heavy metal elements and reactivity, however but without toxicity, danger caused by these heavy metals and
Environmental issue；（3）Some important organic hypervalent iodine reagent such as PIDA, PIFA, DMP have been commercialized, and certain reagents also can root
It is made by easy method according to pertinent literature.Based on advantage possessed by organic hypervalent iodine reagent with us to such reagent
Understand, understanding, we have designed and synthesized electrophilic type trifluoromethylthio transfer examination of the first case based on organic trivalent iodine compound
Agent 1- (trifluoromethylthio)-nitrogen-acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one.
Invention content
The purpose of the present invention is to provide a kind of novel trifluoromethylthio transfering reagent compound 1- (trifluoromethylthio)-
Nitrogen-acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one and its synthetic method, it can overcome the shortcomings of prior art.Due to iodonium
Oxidisability possessed by reagent, reactivity possessed by the reagent have bright with current existing trifluoromethylthio transfering reagent
Aobvious difference.The trifluoromethylthio transfering reagent that the present invention obtains has synthesis convenient, and raw material is easy to get, and has a wide range of application etc. many
Advantage, and recyclable regeneration after the completion of reaction, meet the requirement of Green Chemistry.It is expected that before it should have prodigious application
Scape.
Trifluoromethylthio transfering reagent compound 1- (trifluoromethylthio)-nitrogen provided by the invention-acetyl group -1,2- benzene iodine
Amide -3 (1H) -one (2-acetyl-1- ((trifluoromethyl) thio) -1,2-dihydro-3H-1λ3-benzo[d]
[1,2] iodazol-3-one) structure it is as follows：
Wherein, R=hydrogen, nitro, halogen, cyano, trifluoromethyl, methyl and methoxyl group.
Trifluoromethylthio transfering reagent compound 1- (trifluoromethylthio)-nitrogen provided by the invention-acetyl group -1,2- benzene iodine
Amide -3 (1H) -one structure it is as follows：
The synthetic method of trifluoromethylthio transfering reagent compound 1 provided by the invention includes the steps that：
1）With the chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one class compound 2 and trifluoromethylthio silver（AgSCF3）For
Raw material can be obtained trifluoromethylthio transfering reagent 1 by ligand exchange reaction, and steps are as follows：
Wherein, under nitrogen protection, using organic solvent（Such as chloroform）, at room temperature uniformly by compound 2 and trifluoromethylthio silver
Mixing, is stirred to react 1-2 hours, is filtered to remove silver chlorate and can be obtained trifluoromethylthio transfering reagent.Compound 2 and fluoroform
The molar ratio of sulfenyl silver is 1:1-1.3.
2）The chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one class compound 2 synthetic method be withNAcetyl group
Adjacent iodobenzamide class compound 3 and t-butyl hypochlorate are raw material, can be obtained compound 2 by oxidation reaction.
Wherein, organic solvent is used at room temperature（Such as chloroform）, compound 3 and t-butyl hypochlorate are uniformly mixed, stirred
Reaction 12 hours is mixed, filtering can be obtained compound 2.The compound 3 and the molar ratio of t-butyl hypochlorate are 1:1.2-
1.5。
3）NThe synthetic method of acetyl group neighbour's iodobenzamide class compound 3 is with adjacent 4 He of iodobenzamide class compound
Acetic anhydride is raw material, can be obtained compound 3 by microwave reaction under concentrated sulfuric acid catalyst.
Wherein, compound 4 and acetic anhydride are uniformly mixed, the catalytic amount concentrated sulfuric acid is added, is stirred at 100 DEG C using 50W microwaves
3-10 min are reacted, compound 3 can be obtained by column chromatography purifying.The compound 4 and the molar ratio of acetic anhydride are 1:
3-4.The compound 4 and the molar ratio of the concentrated sulfuric acid are 1:0.01-0.03.
Trifluoromethylthio transfering reagent 1- (trifluoromethylthio)-provided by the invention based on organic trivalent iodine compound
Nitrogen-acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one is a kind of novel electrophilic trifluoromethylthio transfering reagent, there is one kind
It is novelNAcetyl basic ring iodoxy amine skeleton.The reagent has synthetic method simple, and raw material is simple and easy to get, and operation is easy,
Product yield is high, and substrate spectrum is wide, recyclable regeneration, it is environmentally protective many advantages, such as.Tradition can be overcome to be introduced into molecule
The defects of severe reaction conditions possessed by trifluoromethylthio technology, reagent toxicity is strong, inconvenient, and suitable substrates are limited.This
Invention provides a new way for the extensive use of organic trivalent iodine reagent and the molecule containing trifluoromethylthio and commercial synthesis
Diameter, it is contemplated that Social benefit and economic benefit is notable.
Description of the drawings
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of 1 product trifluoromethylthio transfering reagent of example.
Fig. 2 is the carbon-13 nmr spectra figure of 1 product trifluoromethylthio transfering reagent of example.
Fig. 3 is the Enantiomeric excess figure of 1 product trifluoromethylthio transfering reagent of example.
Fig. 4 is the chloro- nitrogen of 2 product 1- of example-acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one hydrogen nuclear magnetic resonance spectrogram.
Fig. 5 is the chloro- nitrogen of 2 product 1- of example-acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one carbon-13 nmr spectra figure.
Fig. 6 is the hydrogen nuclear magnetic resonance spectrogram of 2 product N- acetyl group neighbour's iodobenzamides of example.
Fig. 7 is the carbon-13 nmr spectra figure of 2 product N- acetyl group neighbour's iodobenzamides of example.
Specific implementation mode:
Further detailed, complete explanation is done to the present invention with reference to specific embodiment.
In following embodiments involved specific experiment method and apparatus unless otherwise specified, be conventional method or according to
The condition of manufacturer's specification suggestion is implemented；Involved reagent is commercially available.
Embodiment 1：The synthesis of trifluoromethylthio transfering reagent
Under nitrogen protection, by the chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyl amine -3 (1H) -one（5 mmol, 1.62 g）, new to steam
Chloroform（15 mL）, trifluoromethylthio silver（6 mmol, 1.25 g）It is added sequentially to be placed with two mouthfuls of 50 mL of stirrer in advance
In round-bottomed flask, stir at room temperature 1.5 hours, after reaction, filtering, filtrate is spin-dried for, obtains crude product, add a small amount of dichloro
Methane has just been dissolved to solid, and adding bulk petroleum ether makes it be precipitated out, and filtering can be obtained trifluoromethylthio transfer examination
Agent, yield 80%.Products obtained therefrom is colorless solid, and fusing point is 131 DEG C；1H NMR (400 MHz, CDCl3) δ: 8.48
(d, J = 8.4 Hz, 1H), 8.26 (dd, J = 7.5, 1.6 Hz, 1H), 7.89 (td, J = 7.2, 1.6
Hz, 1H), 7.79 (t, J = 7.2 Hz, 1H), 2.63 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
176.7, 161.3, 136.2, 135.0, 132.4, 131.7, 130.5 (q, J = 309 Hz), 127.1,
113.1, 26.1. 19F NMR(376 MHz, CDCl3) δ: -29.66 (s, 3F).
Embodiment 2：The chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one synthesis
It willNAcetyl group neighbour's iodobenzamide（40 mmol, 11.56 g）, chloroform（60 mL）, t-butyl hypochlorate（60
mmol, 6.54 g）It is added sequentially to be placed in advance in 100 mL round-bottomed flasks of stirrer, stir 12 hours at room temperature, reaction
After, filtering, filter cake can be obtained the chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyl amine -3 (1 with a small amount of chloroformH) -one, production
Rate is 94%.Products obtained therefrom is colorless solid, 183 DEG C of decomposition temperature；1H NMR (400 MHz, DMSO-d 6 ) δ:8.43
(d, J = 8.3 Hz, 1H), 8.20-8.02 (m, 2H), 7.88 (t, J = 7.3 Hz, 1H), 2.56 (s,
3H). 13C NMR (100 MHz, DMSO-d 6 ) δ: 174.4, 161.9, 136.9, 134.4, 131.8, 131.6,
128.1, 115.0, 25.4.
Embodiment 3：NThe synthesis of acetyl group neighbour's iodobenzamide
By adjacent iodobenzamide（40 mmol, 9.88 g）, acetic anhydride（120 mmol, 12.24 g）, the concentrated sulfuric acid（1 mL）Successively
It is added to and is placed in 40 mL microwave reaction pipes of stirrer in advance, 50W microwaves are used at 100 DEG C, react 10 minutes, reaction knot
Shu Hou is added saturated sodium bicarbonate solution and washes away acetic acid, ethyl acetate extraction, and column chromatography can be obtained after purificationNAcetyl group is adjacent
Iodobenzamide, yield 90%.Products obtained therefrom is colorless solid；1H NMR (400 MHz, CDCl3) δ：8.92 (s,
1H), 7.86 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 4.4 Hz, 2H), 7.15-7.11 (m, 1H),
2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 172.6, 167.8, 140.1, 139.9, 132.0,
128.2, 128.1, 91.9, 25.3.
With different substituent group (including nitro, cyano, halogen, trifluoromethyl, methyl and first on adjacent iodobenzamide phenyl ring
Oxygroup) when, it prepares correspondingNThe experimental method of acetyl group neighbour's iodobenzamide derivative is same as above.
Claims (8)
1. a kind of trifluoromethylthio transfering reagent compound 1- (trifluoromethylthio)-nitrogen-acetyl group -1,2- benzenesulfonyls amine -3
(1H) -one, it is characterised in that its structure is as follows：
Wherein, R=hydrogen, nitro, halogen, cyano, trifluoromethyl, methyl and methoxyl group.
2. trifluoromethylthio transfering reagent compound described in accordance with the claim 1, it is characterised in that its structure is：
。
3. trifluoromethylthio transfering reagent compound described in accordance with the claim 1, it is characterised in that its structure is：
。
4. the synthetic method of the trifluoromethylthio transfering reagent compound described in claim 2, it is characterised in that include the steps that：
1）With the chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one class compound 2 and trifluoromethylthio silver is raw material, lead to
It crosses ligand exchange reaction and can be obtained trifluoromethylthio transfering reagent 1, steps are as follows：
Wherein, under nitrogen protection, using organic solvent, at room temperature by compound 2 and the uniformly mixing of trifluoromethylthio silver, stirring
Reaction 1-2 hours, is filtered to remove silver chlorate and can be obtained trifluoromethylthio transfering reagent；
2）The chloro- nitrogen of 1--acetyl group -1,2- benzenesulfonyls amine -3 (1H) -one class compound 2 synthetic method be withNAcetyl group neighbour's iodine
Benzamide compound 3 and t-butyl hypochlorate are raw material, can be obtained compound 2 by oxidation reaction, wherein in room temperature
It is lower to use organic solvent, compound 3 and t-butyl hypochlorate are uniformly mixed, are stirred to react 12 hours, can be obtained is filtered
Close object 2；
3）NThe synthetic method of acetyl group neighbour's iodobenzamide class compound 3 is with adjacent iodobenzamide class compound 4 and acetic acid
Acid anhydride is raw material, can be obtained compound 3 by microwave reaction under concentrated sulfuric acid catalyst；
Wherein, compound 4 and acetic anhydride are uniformly mixed, the catalytic amount concentrated sulfuric acid is added, is stirred at 100 DEG C using 50W microwaves
3-10 min are reacted, compound 3 can be obtained by column chromatography purifying.
5. synthetic method described in accordance with the claim 3, feature is chloroform in the organic solvent.
6. synthetic method described in accordance with the claim 3, it is characterised in that step 1）The compound 2 and trifluoromethylthio silver
Molar ratio be 1:1-1.3.
7. synthetic method described in accordance with the claim 3, it is characterised in that step 2）The compound 3 and t-butyl hypochlorate
Molar ratio be 1:1.2-1.5.
8. synthetic method described in accordance with the claim 3, it is characterised in that step 3）Mole of the compound 4 and acetic anhydride
Than being 1:3-4；The compound 4 and the molar ratio of the concentrated sulfuric acid are 1:0.01-0.03.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303115A (en) * | 2020-03-04 | 2020-06-19 | 南开大学 | Organic trivalent iodine monofluoro transfer reagent compound and synthetic method thereof |
| CN111718323A (en) * | 2020-07-10 | 2020-09-29 | 南宁师范大学 | High-valence iodothiocyanide reagent and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804348A (en) * | 2012-11-15 | 2014-05-21 | 中国科学院上海有机化学研究所 | Electrophilic fluoroform sulfenyl reagent and synthetic method and application thereof |
-
2018
- 2018-02-26 CN CN201810158577.3A patent/CN108299384A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804348A (en) * | 2012-11-15 | 2014-05-21 | 中国科学院上海有机化学研究所 | Electrophilic fluoroform sulfenyl reagent and synthetic method and application thereof |
Non-Patent Citations (7)
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303115A (en) * | 2020-03-04 | 2020-06-19 | 南开大学 | Organic trivalent iodine monofluoro transfer reagent compound and synthetic method thereof |
| CN111718323A (en) * | 2020-07-10 | 2020-09-29 | 南宁师范大学 | High-valence iodothiocyanide reagent and preparation method and application thereof |
| CN111718323B (en) * | 2020-07-10 | 2021-06-11 | 南宁师范大学 | High-valence iodothiocyanide reagent and preparation method and application thereof |
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