CN109836365A - The thio acyl fluorides derivative of a kind of amine and its synthetic method - Google Patents

The thio acyl fluorides derivative of a kind of amine and its synthetic method Download PDF

Info

Publication number
CN109836365A
CN109836365A CN201910034306.1A CN201910034306A CN109836365A CN 109836365 A CN109836365 A CN 109836365A CN 201910034306 A CN201910034306 A CN 201910034306A CN 109836365 A CN109836365 A CN 109836365A
Authority
CN
China
Prior art keywords
nmr
amine
derivative
cdcl
acyl fluorides
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.)
Granted
Application number
CN201910034306.1A
Other languages
Chinese (zh)
Other versions
CN109836365B (en
Inventor
姜丽琴
甄龙
蔡忠良
姚智
杨俊�
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.)
East China Normal University
Original Assignee
East China Normal 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 East China Normal University filed Critical East China Normal University
Priority to CN201910034306.1A priority Critical patent/CN109836365B/en
Publication of CN109836365A publication Critical patent/CN109836365A/en
Application granted granted Critical
Publication of CN109836365B publication Critical patent/CN109836365B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

The invention discloses the thio acyl fluorides derivative of a kind of amine and its synthetic method, the derivative has formula (I) structure；Its synthetic method 1: using secondary amine, trifluoromethyl trimethylsilane, sulphur and potassium fluoride as raw material, using organic solvent as solvent, after reacted at room temperature, the thio acyl fluorides derivative of amine is obtained.The thio acyl fluorides derivative of amine of the present invention, has many advantages, such as that easy to operate, safe and efficient, reaction condition is mild, and raw material is easy to get and cheap.Synthetic method 2: using secondary amine, fluoroform sulphur silver and potassium bromide as raw material, using organic solvent as solvent, after reacted at room temperature, the thio acyl fluorides derivative of amine is obtained.The thio acyl fluorides derivative of amine of the present invention has many advantages, such as that easy to operate, safe and efficient, raw material is easy to get, almost quantitative yield, substrate applicability are wide, modifies after can be used for drug or complex compound selectivity.

Description

The thio acyl fluorides derivative of a kind of amine and its synthetic method
Technical field
The invention belongs to synthesize medicine, chemical field, the thio acyl fluorides derivative of a kind of amine and its synthetic method are related generally to.
Background technique
Tradition prepares the thio acyl fluorides of amine and needs the thio phosgene of high poison or the chlorine of high poison, and therefore, tradition is prepared Substance of this kind it is very limited.
Chemist is using safe reagent (Me in recent years4N)SCF3Or Ph3P+CF2CO2-(PDFA) and sulphur and secondary amine Reaction preparation, and one pot is derived as trifluoromethyl amine derivative.But it expensive starting materials or is not easy to obtain.The thio acyl fluorides of amine and amine are thio Acyl chlorides is compared, and electrophilicity weakens, to have better substrate compatibility and selectivity.If cheap and easily-available raw material system can be used The standby thio acyl fluorides of amine for providing extensive substrate spectrum and functional group's compatibility will become important organic synthesis intermediate to it It plays a positive role.
Summary of the invention
The shortcomings that the present invention overcomes in the presence of prior art synthetic method, using it is simple, be easy to get, cheaply, stablize Nontoxic reagent is raw material, has synthesized the thio acyl fluorides derivative of amine.The method one of the thio acyl fluorides derivative of this synthesis amine has original Expect simple and easy to get, nontoxic, operating method is simple, safe and convenient, condition as mild as a dove, efficiently, the advantages that yield is good.This synthesis The method two of the thio acyl fluorides derivative of amine is with raw material is easy to get, is safe and efficient, raw material is easy to get, almost quantitative yield, substrate are applicable in Property is wide, can be used for after drug or complex compound selectivity the advantages that modifying.
The invention proposes the thio acyl fluorides derivative of a kind of amine, which has formula:
Wherein,
R1For rubigan, o-methoxyphenyl, p-methylphenyl, p-bromophenyl, p-trifluoromethyl phenyl, to fluorobenzene Base, o-fluorophenyl, 2- naphthalene, to acetylphenyl, para Toluic Acid's ethoxycarbonyl, phenyl, to N, N- (dimethylamino) Ethylamino benzonitrile perester radical, to N- aminomethyl phenyl, to N, N- 3,5-dimethylphenyl, cyclohexyl, benzyl, 3- thienyl, hexyl, butyl, Isopropyl or 2- pyridyl group；
R2For methyl, ethyl, benzyl, hexyl, isopropyl, butyl, cyclohexyl or phenethyl；
Alternatively, R1-NH-R2For pyrrolidines, piperidines, morpholine, thiomorpholine, amoxapine, totokaine, piperazine or dihydro Yin Diindyl.
The invention proposes the synthetic methods 1 and method 2 of the thio acyl fluorides derivative of amine.
The synthetic method 1 of a kind of thio acyl fluorides derivative of amine, this method is with secondary amine, trifluoromethyl trimethylsilane, sulphur Sulphur and potassium fluoride are raw material, using organic solvent as solvent, after reacting at room temperature, obtain the thio acyl fluorides of amine as shown in formula (I) Derivative；Fluorine derivative,
The synthetic reaction is as shown in reaction formula (I):
Wherein,
R1For rubigan, o-methoxyphenyl, p-methylphenyl, p-bromophenyl, p-trifluoromethyl phenyl, to fluorobenzene Base, o-fluorophenyl, 2- naphthalene, to acetylphenyl, para Toluic Acid's ethoxycarbonyl, phenyl, to N, N- (dimethylamino) Ethylamino benzonitrile perester radical, to N- aminomethyl phenyl, to N, N- 3,5-dimethylphenyl, cyclohexyl, benzyl, 3- thienyl, hexyl, butyl, Isopropyl or 2- pyridyl group；
R2For methyl, ethyl, benzyl, hexyl, isopropyl, butyl, cyclohexyl or phenethyl；
Alternatively, R1-NH-R2For pyrrolidines, piperidines, morpholine, thiomorpholine, amoxapine, totokaine, piperazine or dihydro Yin Diindyl.Wherein:
Specific synthesis process: first by the secondary amine, potassium fluoride, sulphur, the organic solvent is added under nitrogen protection In, trifluoromethyl trimethylsilane is then added, at room temperature, reacts 1-12 hours, it is thio that reaction obtains amine shown in formula (I) Acyl fluorides derivative；
The molar ratio of the raw material is secondary amine: trifluoromethyl trimethylsilane: sulphur: potassium fluoride=1: 5-10: 4-8: 3-6.The organic solvent is n,N-Dimethylformamide or tetrahydrofuran.
The synthetic method 1 of the thio acyl fluorides derivative of amine proposed by the present invention, secondary amine, trifluoromethyl trimethylsilane, fluorine Change potassium, sulphur as raw material, using organic solvent as solvent, after reacting at room temperature, obtains the thio acyl fluorides of amine as shown in formula (I) and spread out Biology.The reaction mechanism is as follows for method according to the present invention, sulphur, and trifluoromethyl trimethylsilane and potassium fluoride are in tetrahydro furan It mutters middle generation fluoroform sulphur potassium (1), fluoroform sulphur potassium is decomposed into potassium fluoride and thio fluorophosgene (2), secondary amine and thio fluorine light Gas is raw to claim target product (3).
The synthetic method 2 of a kind of thio acyl fluorides derivative of amine, this method are original with secondary amine, fluoroform sulphur silver and potassium bromide Material after reacting at room temperature, is obtained such as the thio acyl fluorides derivative of amine shown in formula (I) using organic solvent as solvent.
The synthetic reaction is as shown in reaction formula (II):
Wherein,
R1For phenyl, m-methoxyphenyl, 2- naphthalene, chlorphenyl, Chloro-O-Phenyl, o-bromophenyl, to trifluoromethylbenzene Base, p-nitrophenyl, to cyano-phenyl, to acetylphenyl, 2- pyridyl group, 3- thienyl, benzyl or to N, N- (dimethylamino Base) ethylamino benzonitrile perester radical；
R2For methyl or butyl；
Alternatively, R1-NH-R2For amoxapine, thiomorpholine or totokaine；
Specific synthesis process: first the secondary amine, fluoroform sulphur silver and potassium bromide are dissolved in organic solvent, at room temperature It is derivative to obtain the thio acyl fluorides of amine shown in formula (I) for reaction；
The molar ratio of the raw material is secondary amine: fluoroform sulphur silver: potassium bromide=1: 1.5-3: 1.5-3.
The organic solvent is acetonitrile, methylene chloride, n,N-Dimethylformamide, tetrahydrofuran, dimethyl sulfoxide, first Benzene, Isosorbide-5-Nitrae dioxane or 1,2- dichloroethanes.
The synthetic method 2 of the thio acyl fluorides derivative of amine proposed by the present invention, with secondary amine, fluoroform sulphur silver, potassium bromide, with Organic solvent is solvent, after reacting at room temperature, is obtained such as the thio acyl fluorides derivative of amine shown in formula (I).It is involved in the present invention Method the reaction mechanism is as follows, fluoroform sulphur silver and haloid such as bromination nak response, obtain precipitating silver bromide with it is soluble Fluoroform sulphur potassium (4), fluoroform sulphur potassium can scene be decomposed into thio fluorophosgene and potassium fluoride (5), secondary amine and be formed in situ Thio fluorophosgene reacts to obtain the thio acyl fluorides derivative (6) of amine.
Synthetic method 1 or synthetic method 2 described above, further, the thio acyl fluorides of the amine that reaction is obtained are derivative Object is isolated and purified.
Described isolate and purify be with volume ratio is ethyl acetate: the solution of petroleum ether 1: 100~10 carries out column chromatography.
The invention avoids this hypertoxic reactants with thio phosgene, and avoid the separation of intermediate, use letter Singly be easy to get (be easy preparation or purchase), and the raw material that can be stabilized or store, room temperature as mild as a dove under conditions of efficiently make For the thio acyl fluorides derivative of amine.This method has easy to operate, safety, efficiently, chemo-selective height, step economy, substrate The advantages that range is wide, and functional group's compatibility is wide.
Detailed description of the invention
Fig. 1-126 is the nuclear magnetic resonance of the thio acyl fluorides derivative of 1-42 of embodiment of the present invention amine1H NMR、19F NMR、13C NMR spectra figure.
Specific embodiment
In conjunction with following specific embodiments and attached drawing, the present invention is described in further detail, protection content of the invention It is not limited to following embodiment.Without departing from the spirit and scope of the invention, those skilled in the art it is conceivable that change Change and advantage is all included in the present invention, and using appended claims as protection scope.
Embodiment 1
Method 1: 10mL tetrahydrofuran and fluoroform is added in potassium fluoride (3mmol), sulphur (4mmol) under nitrogen protection Base trimethyl silane (5mmol), the methylphenylamine (1mmol) being then dissolved in (10ml) in tetrahydrofuran are added drop-wise to In reaction system, reaction system at room temperature, after being added dropwise, stirs 1 hour, solvent is removed under reduced pressure, obtains crude product, tie Shown in structure such as formula (2-1).Crude product progress column chromatography (ethyl acetate: petroleum ether=1:100) is obtained into net product, yield is 92%.(1. are same as above condition, when solvent is DMF, yield 50%；2. ibid condition, when sulphur is 8 equivalent, yield is 91%；3. ibid condition, when potassium fluoride is 6 equivalent, yield 90%；4. ibid condition, works as trifluoromethyl trimethylsilane When, yield 91%) method 2:N- methylaniline (0.2mmol) is dissolved in acetonitrile (2mL), KBr (0.3mmol), AgSCF3 (0.3mmol) is added in acetonitrile (2mL), and the N-methyl aniline being then dissolved in (2.0ml) in acetonitrile is added drop-wise to instead It answers in system, reaction system is at 25 DEG C, after being added dropwise, stirs 1 hour, solvent is removed under reduced pressure, obtains crude product, structure As shown in formula (2-1).Crude product progress column chromatography (ethyl acetate: petroleum ether=1:1) is obtained into net product.Yield is 83% (1. are same as above condition, and when potassium bromide is 3 equivalent, fluoroform sulphur silver is 3 equivalents, yield 82%；).Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 1-3,2a ': 2a "=5:1 of product:1H NMR(500MHz,CDCl3)δ7.52–7.31 (m,5H+3H,2a’+2a”),7.25–7.14(m,2H,2a’),3.66(s,3H,2a’),3.49(s,3H,2a”).19F NMR (471MHz,CDCl3)δ21.59(2a’),20.07(2a”).13C NMR(126MHz,CDCl3) δ 182.32 (d, J= 319.7Hz, 2a "), 180.61 (d, J=319.7Hz, 2a '), 144.15 (2a "), 141.10 (2a '), 129.91 (2a "), 129.64 (2a '), 128.65 (2a "), 128.53 (2a '), 125.93 (d, J=1.5Hz), 124.87 (d, J=1.1Hz, 2a '), 44.86 (d, J=7.2Hz, 2a '), 40.87 (d, J=4.7Hz, 2a ")
HRMS(EI)m/z calculated for C8H8FNS[M]+169.0361,found 163.0364。
Embodiment 2
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- methyl P-nethoxyaniline, obtained product As shown in structural formula (2-2).Yield is 94%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as Figure 4-Figure 6, product 2b ': 2b "=5:1:1H NMR(500MHz,CDCl3) δ 7.26 (d, J=9.7Hz, 2H, 2b "), 7.12 (d, J=8.5Hz, 2H, 2b '), 6.97 (d, J=9.0Hz, 2H, 2b "), 6.94-6.91 (m, 2H, 2b '), 3.83 (s, 3H, 2b "), 3.82 (s, 3H, 2b '), 3.63 (s, 3H, 2b '), 3.47 (d, J=2.5Hz, 3H, 2b ")19F NMR(471MHz,CDCl3)δ21.28(2b’), 19.86(2b”).13C NMR(126MHz,CDCl3) δ 182.59 (d, J=319.7Hz, 2b "), 180.89 (d, J=319.7Hz, 2b '), 159.32 (2b+2b "), 136.99 (2b "), 133.89 (2b '), 126.98 (d, J=1.9Hz, 2b "), 125.95 (2b '), 115.01 (2b "), 114.72 (2b '), 55.58 (2b "), 55.52 (2b '), 45.07 (d, J=7.3Hz, 2b '), 41.07 (d, J=4.7Hz, 2b ")
HRMS(EI)m/z calculated for C9H10NOFS[M]+199.0467,found 199.0470。
Embodiment 3:
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- methyl m-anisidine, obtained product As shown in structural formula (2-3), 1 yield of method is 90%.The present embodiment is identical as 1 method 2 of embodiment, and amine is only changed to N- methyl M-anisidine, 2 yield of method are 98%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as Figure 7-9, product 2c ': 2c "=6:1:1H NMR(500MHz,CDCl3) δ 7.38 (t, J=8.2Hz, 1H, 2c "), 7.33 (t, J=8.1Hz, 1H, 2c '), 6.95-6.88 (m, 1H+1H, 2c '+2c "), 6.80 (d, J=7.9Hz, 1H+1H, 2c '+2c "), 6.74 (s, 1H+1H, 2c '+2c "), 3.82 (s, 3H, 2c '), 3.64 (s, 3H, 2c '), 3.48 (d, J=1.7Hz, 3H, 2c "), 2.93 (s, 3H, 2c”).19F NMR(471MHz,CDCl3)δ21.82(2c’),20.22(2c”).13C NMR(126MHz,CDCl3)δ182.13 (d, J=324.3Hz, 2c "), 180.62 (d, J=320.0Hz, 2c '), 160.61 (2c "), 160.36 (2c '), 145.10 (2c”),142.07(2c’),130.68(2c”),130.34(2c’),117.90(2c”),116.98(2c’),114.22 (2c "), 114.10 (2c '), 111.90 (2c "), 110.92 (2c '), 55.55 (2c '+2c "), 44.81 (d, J=7.2Hz, 2c '), 40.86 (d, J=4.5Hz, 2c ")
HRMS(EI)m/z calculated for C9H10NOFS[M]+199.0467,found 199.0468。
Embodiment 4
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- methyl o-aminoanisole, obtained product As shown in structural formula (2-4), yield 97%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 10-12, produces 2d ': 2d "=6:1 of object:1H NMR(500MHz,CDCl3) δ 7.39 (dd, J=7.7,1.1Hz, 1H, 2d "), 7.37-7.33 (m, 1H, 2d '), 7.28 (d, J=10.1Hz, 1H, 2d "), 7.15 (dd, J=8.0,1.5Hz, 1H, 2d '), 7.02 (dd, J=7.7, 5.3Hz,2H,2d”),7.01–6.96(m,2H,2d’),3.88(s,3H,2d”),3.86(s,3H,2d’),3.56(s,3H, 2d '), 3.40 (d, J=2.3Hz, 3H, 2d ")19F NMR(471MHz,CDCl3)δ20.67(2d’),17.64(2d”).13C NMR(126MHz,CDCl3) δ 182.65 (d, J=324.6Hz, 2d "), 181.61 (d, J=319.1Hz, 2d '), 153.77 (2d”),153.42(2d’),132.38(2d”),130.29(2d”),130.23(2d’),129.62(2d’),127.83 (2d”),126.67(2d’),121.28(2d”),120.89(2d’),112.72(2d”),112.16(2d’),55.87(2d”), 55.81 (2d '), 43.91 (d, J=7.3Hz, 2d '), 39.69 (d, J=4.4Hz, 2d ")
HRMS(EI)m/z calculated for C9H10NOFS[M]+199.0467,found 199.0469。
Embodiment 5:
The present embodiment is identical as 1 method 1 of embodiment, amine is only changed to N- methyl para-totuidine, obtained product is as tied Shown in structure formula (2-5), yield 97%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as illustrated in figs. 13-15, product 2e ': 2e "=5:1:1H NMR(500MHz,CDCl3) δ 7.27 (d, J=9.1Hz, 2H, 2e "), 7.23 (d, J=8.1Hz, 2H+ 2H, 2e '+2e "), 7.09 (d, J=8.1Hz, 2H, 2e '), 3.64 (s, 3H, 2e '), 3.47 (d, J=2.4Hz, 3H, 2e "), 2.39(s,3H,2e”),2.38(s,3H,2e’).19F NMR(471MHz,CDCl3)δ21.32(2e’),19.85(2e”).13C NMR(126MHz,CDCl3) δ 182.40 (d, J=324.6Hz, 2e "), 180.75 (d, J=319.4Hz, 2e '), 141.65 (s2e "), 138.72 (2e "), 138.60 (d, J=2.6Hz, 2e '), 130.51 (2e "), 130.18 (2e '), 125.56 (d, J =1.7Hz, 2e "), 124.56 (d, J=0.9Hz, 2e '), 44.91 (d, J=7.3Hz, 2e '), 40.90 (d, J=4.7Hz, 2e”),21.23(2e”),21.09(2e’).
HRMS(EI)m/z calculated for C9H10NFS[M]+183.0518,found 183.0519。
Embodiment 6
The present embodiment is identical as 1 method 1 of embodiment, amine is only changed to N- methyl meta-aminotoluene, obtained product is as tied Shown in structure formula (2-6), yield 99%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 16-18, product 2f ': 2f "=6:1:1H NMR(500MHz,CDCl3) δ 7.38-7.33 (m, 1H, 2f "), 7.31 (t, J=7.7Hz, 1H, 2f '), 7.22-7.12 (m, 1H+3H, 2f '+2f "), 7.01 (d, J=11.5Hz, 2H, 2f '), 3.64 (s, 3H, 2f '), 3.47 (d, J= 2.4Hz,3H,2f”),2.39(s,3H,2f”),2.38(s,3H,2f’).19F NMR(471MHz,CDCl3)δ21.49(2f’), 19.85(2f”).13C NMR(126MHz,CDCl3) δ 182.27 (d, J=323.9Hz, 2f "), 180.65 (d, J=319.5Hz, 2f’),144.08(2f”),141.05(2f’),140.09(2f”),139.83(2f’),129.70(2f”),129.45(2f”), 129.39 (2f '), 129.29 (2f '), 126.34 (2f "), 125.42 (2f '), 122.85 (2f "), 121.82 (d, J= 0.8Hz, 2f '), 44.87 (d, J=7.2Hz, 2f "), 40.89 (d, J=4.7Hz, 2f '), 21.34 (2f "), 21.28 (2f ')
HRMS(EI)m/z calculated for C9H10NFS[M]+183.0518,found 183.0516。
Embodiment 7
The present embodiment is identical as 1 method 1 of embodiment, amine is only changed to N- methyl ortho-aminotoluene, obtained product is as tied Shown in structure formula (2-7), yield 92%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 19-21, product 2a ': 2a "=4:1:1H NMR(500MHz,CDCl3) δ 7.34-7.23 (m, 3H+3H, 2g '+2g "), 7.20 (d, J=6.8Hz, 1H, 2g "), 7.12 (d, J=7.6Hz, 1H, 2g '), 3.57 (s, 3H, 2g '), 3.42 (s, 3H, 2g "), 2.29 (s, 3H, 2g "), 2.25(s,3H,2g’).19F NMR(471MHz,CDCl3)δ21.40(s,2g’),17.27(s,2g”).13C NMR(126MHz, CDCl3) δ 181.50 (d, J=318.4Hz, 2g "), 180.98 (d, J=318.4Hz, 2g ') .142.53 (2g "), 140.17 (2g’),134.13(2g”),133.85(2g’),131.74(2g”),131.43(2g’),129.15(2g”),129.13 (2g '), 127.82 (2g "), 127.35 (2g '), 125.90 (d, J=1.8Hz, 2g "), 125.31 (2g '), 43.95 (2g '), 39.82 (d, J=4.2Hz, 2g "), 17.20 (2g "), 17.19 (2g ')
HRMS(EI)m/z calculated for C9H10NFS[M]+183.0518,found 183.0517。
Embodiment 8
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N1, N1, N4Trimethyl p-phenylenediamine, it is obtained Shown in product such as structural formula (2-8), yield 60%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra such as Figure 22-24 institute Show, 2h ': 2h "=6:1 of product.1H NMR(500MHz,CDCl3) δ 7.17 (d, J=8.8Hz, 2h ', 2h "), 7.04 (d, J= 8.8Hz, 2h ', 2h '), 6.72 (d, J=8.9Hz, 2h ', 2h "), 6.68 (d, J=8.9Hz, 2h ', 2h '), 3.62 (s, 3H, 2h '), 3.45 (d, J=2.2Hz, 3H, 2h "), 2.98 (s, 6H, 2h "), 2.97 (s, 6H, 2h ')19F NMR(471MHz, CDCl3)δ20.40(2h’),19.38(2h”).13C NMR(126MHz,CDCl3) δ 182.64 (d, J=323.9Hz, 2h "), 180.61 (d, J=186.5Hz, 2h '), 150.08 (2h '), 132.88 (2h "), 129.82 (2h '), 126.23 (d, J= 1.8Hz, 2h "), 125.32 (2h '), 112.51 (2h "), 112.27 (2h '), 45.19 (d, J=7.5Hz, 2h '), 41.16 (d, J=4.5Hz, 2h "), 40.42 (2h '), 40.39 (2h ")
HRMS(EI)m/z calculated for C10H13FN2S[M]+212.0783,found 212.0781。
Embodiment 9
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N1, N4Dimethyl-p-phenylenediamine, obtained product As shown in structural formula (2-9), yield 87%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as illustrated in figs. 25-27, produces 2i ': 2i "=5:1 of object.1H NMR(500MHz,CDCl3) δ 7.12 (d, J=8.7Hz, 2H, 2i "), 6.99 (d, J=8.7Hz, 2H, 2i '), 6.62 (d, J=8.6Hz, 2H, 2i "), 6.58 (d, J=8.7Hz, 2H, 2i '), 3.95 (s, 1H+1H, 2i '+ 2i "), 3.61 (s, 3H, 2i '), 3.45 (d, J=2.2Hz, 3H, 2i "), 2.84 (s, 3H+3H, 2i '+2i ")19F NMR (471MHz,CDCl3)δ20.50(2i’),19.36(2i”).13C NMR(126MHz,CDCl3) δ 182.65 (d, J= 324.3Hz, 2i "), 181.13 (d, J=318.1Hz, 2i '), 149.17 (2i '), 133.66 (2i "), 130.52 (2i '), 126.48(2i”),126.27(2i’),125.56(2i’),125.32(2i”),112.67(2i”),112.36(2i’),45.21 (d, J=7.5Hz, 2i '), 41.19 (d, J=4.6Hz, 2i '), 30.57 (2i '), 30.54 (2i ")
HRMS(EI)m/z calculated for C9H11FN2S[M]+198.0627,found 198.0632。
Embodiment 10
The present embodiment is identical as 1 method 1 of embodiment, amine is only changed to N- methylresorcinol base aniline, obtained product is such as Shown in structural formula (2-10), yield 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 28-30, produces 2j ': 2j "=6:1 of object.1H NMR(500MHz,CDCl3) δ 7.64-7.35 (m, 8H+8H, 2j '+2j "), 7.32 (d, J= 8.0Hz, 1H, 2j "), 7.18 (dd, J=7.9,0.8Hz, 1H, 2j '), 3.69 (s, 3H, 2j '), 3.53 (d, J=2.2Hz, 3H, 2j”).19F NMR(471MHz,CDCl3)δ21.91(2j’),20.43(2j”).13C NMR(126MHz,CDCl3)δ182.35 (d, J=324.9Hz, 2j "), 180.64 (d, J=319.8Hz, 2j '), 144.60 (2j "), 143.18 (2j "), 143.07 (2j’),141.60(2j’),139.73(2j”),139.54(2j’),130.27(2j”),130.03(2j’),129.04 (2j’),128.98(2j”),128.13(2j’),128.00(2j”),127.27(2j”),127.23(2j”),127.16 (2j '), 124.78 (2j "), 124.53 (2j "), 123.62 (2j '), 123.53 (2j '), 44.91 (d, J=7.2Hz, 2j '), 40.92 (d, J=4.5Hz, 2j ")
HRMS(EI)m/z calculated for C14H12FNS[M]+245.0674,found 245.0679。
Embodiment 11
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- methyl -2- naphthylamines, obtained product such as structure Shown in formula (2-11), 1 yield of method is 74%.The present embodiment is identical as 1 method 2 of embodiment, and amine is only changed to N- methyl -2- naphthalene Amine, 2 yield of method are 96%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 31-33, product 2k ': 2k " =6:1.1H NMR(500MHz,CDCl3)δ7.95–7.81(m,3H+3H,2k’+2k”),7.79(s,1H,2k”),7.67(d,J =1.0Hz, 1H, 2k '), 7.59-7.50 (m, 2H+2H, 2k '+2k "), 7.46 (dd, J=8.7,1.7Hz, 1H, 2k "), 7.29 (d, J=8.7Hz, 1H, 2k "), 3.74 (s, 3H, 2k '), 3.57 (d, J=2.2Hz, 1H, 2k ")19F NMR(471MHz, CDCl3)δ21.99(2k’),20.19(2k”).13C NMR(126MHz,CDCl3) δ 182.45 (d, J=325.2Hz, 2k "), 180.75 (d, J=319.7Hz, 2k '), 141.46 (2k "), 138.44 (2k '), 133.57 (2k "), 133.20 (2k '), 132.74(2k”),132.56(2k’),130.00(2k”),129.78(2k’),128.11(2k”),128.05(2k’), 127.94(2k”),127.86(2k’),127.25(2k’),127.19(2k’),127.16(2k”),126.97(2k”), 124.51 (2k "), 123.74 (2k "), 123.48 (2k '), 122.70 (d, J=1.1Hz, 2k '), 45.01 (d, J=7.2Hz, 2k '), 41.07 (d, J=4.4Hz, 2k ")
HRMS(EI)m/z calculated for C12H10FNS[M]+219.0518,found 219.0522。
Embodiment 12
Method 1: 10mL tetrahydrofuran and fluoroform is added in potassium fluoride (3mmol), sulphur (4mmol) under nitrogen protection Base trimethyl silane (8mmol), N- methyl parachloroanilinum (1mmol) drop being then dissolved in (10ml) in tetrahydrofuran It being added in reaction system, reaction system at room temperature, after being added dropwise, stirs 1 hour, solvent is removed under reduced pressure, obtains crude product, Shown in its structure such as formula (2-12).Crude product progress column chromatography (ethyl acetate: petroleum ether=1:100) is obtained into net product, is produced Rate is 69%.Method 2 is identical as the method 2 of example 1, and amine is only changed to N- methyl parachloroanilinum, yield 98%.Nuclear-magnetism is total Vibration1H NMR、19F NMR、13C NMR spectra is as shown in Figure 34-36,21 ': 21 "=4:1 of product:1H NMR(500MHz,CDCl3) δ 7.48-7.38 (m, 2H+2H, 2l '+2l "), 7.30 (d, J=8.6Hz, 2H, 21 "), 7.17 (dd, J=8.6,0.8Hz, 2H, 2l '), 3.64 (s, 3H, 21 '), 3.48 (d, J=2.3Hz, 1H, 21 ")19F NMR(471MHz,CDCl3)δ22.14(21’), 20.77(2l”).13C NMR(126MHz,CDCl3) δ 182.27 (d, J=324.0Hz, 2l "), 180.37 (d, J=320.1Hz, 2l’),142.55(2l”),139.51(2l’),134.43(2l”),134.36(2l’),130.15(2l”),129.84(2l’), 127.48 (2l "), 126.28 (d, J=1.1Hz, 2l '), 44.75 (d, J=7.2Hz, 2l '), 40.80 (d, J=4.3Hz, 2l”).
HRMS(EI)m/z calculated for C8H7FNSCl[35][M]+202.9972,found 202.9973。
Embodiment 13
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- methyl m-chloroaniline, obtained product is as tied Shown in structure formula (2-13).Yield is 76%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 37-39, product 2m ': 2m "=5:1.1H NMR(500MHz,CDCl3) δ 7.44-7.35 (m, 2H+3H, 2m '+2m "), 7.27 (d, J=10.9Hz, 1H+1H, 2m '+2m "), 7.15 (dd, J=7.1,1.2Hz, 1H, 2m '), 3.66 (s, 3H, 2m '), 3.51 (s, 3H, 2m ")19F NMR(471MHz,CDCl3)δ22.46(2m’),20.86(2m”).13C NMR(126MHz,CDCl3) δ 182.18 (d, J= 324.2Hz, 2m "), 180.29 (d, J=320.5Hz, 2m '), 145.00 (2m "), 141.98 (2m '), 135.14 (2m '), 130.92(2m”),130.62(2m’),128.94(2m”),128.78(2m’),126.61(2m”),125.40(2m’), 124.46 (2m "), 123.29 (2m '), 44.69 (d, J=7.2Hz, 2m '), 40.78 (2m ")
HRMS(EI)m/z calculated for C8H7FNSCl[35][M]+202.9972,found 202.9974。
Embodiment 14
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to N- methyl o-chloraniline, and time 12h is acquired Product such as structural formula (2-14) shown in, yield 31%.2 yield of method is 91%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 40-42,2n ': 2n "=4:1 of product.1H NMR(500MHz,CDCl3)δ7.56–7.47(m,1H+1H, 2n '+2n "), 7.41-7.32 (m, 2H+3H, 2n '+2n "), 7.28 (dd, J=5.8,3.1Hz, 1H, 2n "), 3.59 (s, 3H, 2n '), 3.45 (d, J=1.9Hz, 1H, 2n ")19F NMR(471MHz,CDCl3)δ23.00(2n’),17.69(2n”).13C NMR(126MHz,CDCl3) δ 182.08 (d, J=326.4Hz, 2n "), 180.97 (d, J=319.6Hz, 2n '), 140.94 (2n”),138.56(2n’),131.21(2n”),130.99(2n’),130.95(2n”),130.68(2n’),130.36 (2n '), 130.30 (2n "), 128.57 (2n "), 128.42 (d, J=1.6Hz, 2n "), 128.16 (2n '), 127.41 (2n '), 43.60 (d, J=7.3Hz, 2n '), 39.55 (d, J=4.0Hz, 2n ").
HRMS(EI)m/z calculated for C8H7FNSCl[35][M]+202.9972,found 202.9975。
Embodiment 15
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- methyl para-bromoaniline, obtained product is as tied Shown in structure formula (2-15), 1 yield of method is 75%.The present embodiment is identical as 1 method 2 of embodiment, and amine is only changed to N- methyl pair Bromaniline, 2 yield of method are 97%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 43-45, product 2o ': 2o "=5:1.1H NMR(500MHz,CDCl3) δ 7.60 (d, J=8.6Hz, 2H, 2o "), 7.58-7.55 (m, 2H, 2o '), 7.25 (d, J=8.5Hz, 2H, 2o "), 7.13-7.08 (m, 2H, 2o '), 3.63 (s, 3H, 2o '), 3.48 (d, J=2.2Hz, 3H, 2o”).19F NMR(471MHz,CDCl3)δ22.18(2o’),2o’.83(2o”).13C NMR(126MHz,CDCl3)δ182.17 (d, J=325.0Hz, 2o "), 180.27 (d, J=320.2Hz, 2o '), 143.05 (2o "), 140.03 (2o '), 133.12 (2o "), 132.83 (2o '), 127.78 (2o "), 126.57 (d, J=1.1Hz, 2o '), 122.44 (2o "), 122.29 (2o '), 44.70 (d, J=7.2Hz, 2o '), 40.74 (d, J=4.4Hz, 2o ")
HRMS(EI)m/z calculated for C8H7FNSBr[79][M]+246.9467,found 246.9464。
Embodiment 16
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- methyl para-fluoroaniline, obtained product is as tied Shown in structure formula (2-16).Yield is 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 46-48, product 2p ': 2p "=5:1.1H NMR(500MHz,CDCl3) δ 7.34 (dd, J=8.2,4.8Hz, 2H, 2p "), 7.21 (dd, J=8.3, 4.9Hz,2H,2p’),7.14(m,2H+2H,2p’+2p”),3.64(s,3H,2p’),3.49(s,3H,2p”).19F NMR (471MHz,CDCl3)δ22.11(2p’),20.44(2p”),-111.80(2p”),-112.12(2p’).13C NMR(126MHz, CDCl3) δ 182.49 (d, J=325.2Hz, 2p "), 180.60 (d, J=319.7Hz, 2p '), 161.97 (d, J=249.3Hz, 2p '+2p "), 140.11 (d, J=3.2Hz, 2p "), 140.11 (d, J=3.2Hz, 2p "), 137.03 (d, J=3.3Hz, 2p '), 127.94 (d, J=8.8Hz, 2p "), 126.77 (d, J=8.7Hz, 2p '), 116.91 (d, J=23.1Hz, 2p "), 116.63 (d, J=23.1Hz, 2p '), 44.92 (d, J=7.2Hz, 2p '), 40.95 (d, J=4.7Hz, 2p ")
HRMS(EI)m/z calculated for C8H7F2NS[M]+187.0267,found 187.0268。
Embodiment 17
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- methyl neighbour's fluoroaniline, obtained product is as tied Shown in structure formula (2-16).Yield is 82%.Shown in obtained product such as structural formula (2-17).Yield is 88%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 49-51,2q ': 2q "=5:1 of product.1H NMR(500MHz,CDCl3)δ 7.39 (tdd, J=7.0,5.3,2.9Hz, 1H+1H, 2q '+2q "), 7.30-7.16 (m, 3H+3H, 2q '+2q "), 3.63 (d, J =6.8Hz, 3H, 2q '), 3.47 (d, J=2.3Hz, 1H, 2q ")19F NMR(471MHz,CDCl3) δ 22.09 (d, J= 5.8Hz, 2q '), 19.25 (2q "), -121.15 (2q "), -121.21 (d, J=5.7Hz, 2q ')13C NMR(126MHz, CDCl3) δ 182.44 (d, J=326.2Hz, 2q "), 180.99 (d, J=320.6Hz, 2q '), 156.86 (d, J=253.3Hz, 2q "), 156.18 (d, J=251.9Hz, 2q '), 131.39 (d, J=12.2Hz, 2q "), 130.71 (d, J=7.9Hz, 2q "), 130.56 (d, J=7.8Hz, 2q '), 128.62 (d, J=13.2Hz, 2q "), 128.37 (2q "), 127.15 (2q '), 125.24 (d, J=3.8Hz, 2q "), 124.95 (d, J=4.0Hz, 2q '), 117.28 (d, J=19.1Hz, 2q "), 117.00 (d, J= 19.5Hz, 2q '), 44.12 (d, J=7.2Hz, 2q '), 40.09 (d, J=2.8Hz, 2q ")
HRMS(EI)m/z calculated for C8H7F2NS[M]+187.0267,found 187.0269。
Embodiment 18
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to N- methyl p-trifluoromethylaniline, obtained production Shown in object such as structural formula (2-18), yield 53%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to N- methyl to three Methyl fluoride aniline, yield 96%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in figs. 52-54, product 2r ': 2r "=5:1.1H NMR(500MHz,CDCl3) δ 7.72 (d, J=8.3Hz, 2H+2H, 2r '+2r "), 7.51 (d, J=6.3Hz, 2H, 2r "), 7.37 (d, J=8.1Hz, 2H, 2r '), 3.68 (s, 3H, 2r '), 3.52 (s, 3H, 2r ")19F NMR(471MHz, CDCl3)δ22.59(2r”),21.52(2r’),62.75(2r’+2r”).13C NMR(126MHz,CDCl3) δ 182.13 (d, J= 324.1Hz, 2r "), 180.12 (d, J=320.7Hz, 2r '), 143.96 (2r '), 130.60 (q, J=33.4Hz, 2r '), 127.11 (2r "), 126.86 (d, J=3.6Hz, 2r '), 125.49 (2r '), 123.47 (q, J=272.5Hz, 2r '), 44.56 (d, J=7.1Hz, 2r '), 40.62 (s, 2r ")
HRMS(EI)m/z calculated for C9H7F4NS[M]+237.0235,found 237.0237。
Embodiment 19
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to N- methyl paranitroaniline, time 12h, gained Shown in the product arrived such as structural formula (2-19), yield 50%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to N- first Base paranitroanilinum, time 12h, yield 98%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra such as Figure 55-57 institute Show, product 2s.1H NMR(500MHz,CDCl3) δ 8.33 (d, J=8.9Hz, 2H, 2s '), 7.46 (s, 2H, 2s '), 3.71 (s, 3H,2s’).19F NMR(471MHz,CDCl3)δ23.13(2s’),22.53(2s”).13C NMR(126MHz,CDCl3)δ 179.65 (d, J=322.2Hz, 2s '), 146.93 (2s '), 146.15 (2s '), 125.98 (2s '), 125.08 (2s '), 44.48(2s’).
HRMS(EI)m/z calculated for C8H7FN2O2S[M]+214.0212,found 214.0217.
Embodiment 20
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to N- methyl to cyano-aniline, time 12h, gained Shown in the product arrived such as structural formula (2-20), yield 52%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to N- first Base is to cyano-aniline, time 12h, yield 96%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra such as Figure 58-60 institute Show, product 2t.1H NMR(500MHz,CDCl3) δ 7.77 (d, J=8.2Hz, 2H+2H, 2t '+2t "), 7.53 (s, 2H, 2t "), 7.39 (d, J=6.0Hz, 2H, 2t '), 3.69 (s, 3H, 2t '), 3.54 (s, 3H, 2t ")19F NMR(471MHz,CDCl3)δ 22.81(2t’),22.45(2t”).13C NMR(126MHz,CDCl3) δ 179.74 (d, J=321.0Hz, 2t '), 144.61 (2t’),133.61(2t’),127.37(2t’),125.93(2t’),117.68(2t’),112.32(2t’),44.47(2t’).
HRMS(EI)m/z calculated for C9H7FN2S[M]+194.0314,found 194.0315.
Embodiment 21
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to N- methyl to Ethyl formate aniline, time 12h, Shown in obtained product such as structural formula (2-21), yield 45%.Method 2 is identical as 1 method 2 of embodiment, is only changed to amine N- methyl is to Ethyl formate aniline, time 12h, yield 97%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is such as Shown in Figure 61-63,2u ': 2u "=6:1 of product.1H NMR(500MHz,CDCl3) δ 8.12 (d, J=8.1Hz, 2H+2H, 2u '+ 2u "), 7.46 (s, 2H, 2u "), 7.31 (d, J=8.1Hz, 2H, 2u '), 4.40 (qd, J=7.1,2.0Hz, 2H+2H, 2u '+ 2u "), 3.68 (s, 3H, 2u '), 3.52 (s, 3H, 2u "), 1.40 (t, J=7.1Hz, 3H+3H, 2u '+2u ")19F NMR (471MHz,CDCl3)δ22.28(2u’),21.29(2u”).13C NMR(126MHz,CDCl3) δ 180.14 (d, J= 320.8Hz,2u’),165.35(2u’),144.65(2u’),131.24(2u”),130.95(2u’),130.43(2u’), 126.14 (2u "), 124.87 (2u '), 61.42 (2u '), 44.57 (d, J=7.0Hz, 2u '), 14.30 (2u ')
HRMS(EI)m/z calculated for C11H12FNO2S[M]+241.0573,found 241.0578.
Embodiment 22
The present embodiment is identical as 12 method 1 of embodiment, and amine is only changed to 2-N- picoline, obtained product such as structure Shown in formula (2-22), yield 71%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to 2-N- picoline, and yield is 99%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 64-66, product 2v.1H NMR(500MHz, CDCl3) δ 8.52 (d, J=4.0Hz, 1H), 7.80 (td, J=7.9,1.9Hz, 1H), 7.41-7.07 (m, 2H), 3.73 (s, 3H).19F NMR(471MHz,CDCl3)δ20.54.13C NMR(126MHz,CDCl3) δ 180.03 (d, J=321.2Hz), 152.58,148.99,138.42,123.07,120.56,42.34.
HRMS(EI)m/z calculated for C7H7FN2S[M]+170.0314,found 170.0313.
Embodiment 23
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to 3-N- methylthiophene, obtained product such as structure Shown in formula (2-23), yield 62%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to 3-N- methylthiophene, and yield is 73%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 67-69,2w ': 2w "=6:1 of product.1H NMR (500MHz,CDCl3) δ 7.40-7.28 (m, 1H+1H, 2w '+2w "), 7.20 (d, J=4.5Hz, 2H, 2w "), 7.15 (s, 1H, 2w '), 7.01 (d, J=4.4Hz, 1H, 2w '), 3.67 (s, 3H, 2w "), 3.50 (s, 3H, 2w ')19F NMR(471MHz, CDCl3)δ22.72(2w”),21.27(2w’).13C NMR(126MHz,CDCl3) δ 180.38 (d, J=321.0Hz, 2w '), 138.46 (2w '), 126.04 (2w '), 125.90 (2w "), 124.35 (2w "), 123.65 (d, J=2.9Hz, 2w '), 119.95 (2w "), 118.19 (2w '), 44.68 (d, J=7.2Hz, 2w '), 40.87 (2w ")
HRMS(EI)m/z calculated for C6H6FNS2[M]+174.9926,found 174.9924.
Embodiment 24
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to indoline, obtained product such as structural formula (2- 24) shown in.Yield is 86%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 70-72, product 2x ': 2x " =4:1.1H NMR (400MHz, CDCl3) δ 8.75 (d, J=8.2Hz, 1H, 2x '), 7.53 (dd, J=8.5,3.2Hz, 1H, 2x”),7.34–7.17(m,3H+2H,2x’+2x”),7.15–7.09(m,1H,2x”),4.33–4.29(m,2H,2x”),4.32 (td, J=12.2,2.1Hz, 2H, 2x '), 3.23-3.19 (m, 2H, 2x "), 3.20-3.16 (m, 2H, 2x ') .13C NMR (101MHz, CDCl3) δ 176.4 (d, J=325.6Hz), 140.0,139.9,132.9,128.2,128.2,127.4,126.4, (125.8,125.0,117.4,117.3,54.1 d, J=6.5Hz), 51.1,26.9,26.6. can not compose the carbon of nuclear magnetic resonance In peak it is corresponding to 2x ' and 2x ", only all peaks are listed.
HRMS(EI)m/z calculated for C9H8FNS[M]+181.0361,found 181.0360。
Embodiment 25
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to Phenhenzamine, obtained product such as structural formula Shown in (2-25), yield 90%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 73-75, product 2y ': 2y "=4:1.1H NMR(500MHz,CDCl3)δ7.42–7.16(m,8H+8H,2y’+2y”),7.13(m,2H,2y”),7.04– 6.98(m,2H,2y’),5.30(s,2H,2y’),4.96(s,2H,2y”).19F NMR(471MHz,CDCl3)δ24.53(2y’), 18.34(2y”).13C NMR(126MHz,CDCl3) δ 181.98 (d, J=324.5Hz, 2y "), 181.60 (d, J=319.9Hz, 2y’),142.76(2y”),139.39(2y’),134.35(2y”),134.28(2y’),129.77(2y”),129.49(2y’), 128.93(2y”),128.74(2y’),128.70(2y’),128.67(2y’),128.53(2y”),128.49(2y”), 128.41 (2y '), 126.98 (2y '), 126.06 (2y '), 60.62 (d, J=6.9Hz, 2y '), 57.63 (d, J=3.3Hz, 2y”).
HRMS(EI)m/z calculated for C14H12FNS[M]+245.0674,found 245.0672。
Embodiment 26
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- benzyl parachloroanilinum, obtained product is as tied Shown in structure formula (2-26), yield 88%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 76-78, product 2z ': 2z "=3:1.1H NMR(500MHz,CDCl3) δ 7.38-7.13 (m, 7H+7H, 2z '+2z "), 7.06 (d, J=8.5Hz, 2H, 2z "), 6.94 (d, J=8.6Hz, 2H, 2z '), 5.28 (s, 2H, 2z "), 4.94 (s, 2H, 2z ')19F NMR(471MHz, CDCl3)δ25.11(2z’),18.65(2z”).13C NMR(126MHz,CDCl3) δ 181.84 (d, J=325.6Hz, 2z "), 181.34 (d, J=320.2Hz, 2z '), 141.05 (2z "), 137.71 (2z '), 134.69 (2z '), 134.00 (2z '), 130.04(2z”),129.72(2z’),129.04(2z”),128.78(2z’),128.67(2z’),128.58(2z’), 128.48 (2z "), 127.45 (2z '), 60.53 (d, J=7.0Hz, 2z '), 57.56 (d, J=2.7Hz, 2z ")
HRMS(EI)m/z calculated for C14H11FNSCl[35][M]+279.0285,found 279.0288。
Embodiment 27
The present embodiment is identical as 12 method 1 of embodiment, amine is only changed to N- hexyl parachloroanilinum, obtained product is as tied Shown in structure formula (2-27), yield 88%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 79-81, product 2aa ': 2aa "=3:1.1H NMR(500MHz,CDCl3) δ 7.45 (d, J=8.6Hz, 2H, 2aa "), 7.43-7.39 (m, 2H, 2aa '), 7.26 (d, J=4.5Hz, 2H, 2aa "), 7.12 (d, J=8.6Hz, 2H, 2aa '), 4.11-3.90 (m, 2H, 2aa '), 3.77 (t, J=7.5Hz, 2H, 2aa "), 1.73-1.59 (m, 2H+2H, 2aa '+2aa "), 1.35-1.24 (m, 6H+6H, 2aa '+ 2aa "), 0.87 (dd, J=8.5,5.1Hz, 3H+3H, 2aa '+2aa ")19F NMR(471MHz,CDCl3)δ25.12(2aa’), 17.46(2aa”).13C NMR(126MHz,CDCl3) δ 182.37 (d, J=324.9Hz, 2aa "), 180.32 (d, J= 320.2Hz,2aa’),141.25(2aa”),138.10(2aa’),134.57(2aa’),130.16(2aa”),129.88 (2aa '), 128.34 (2aa "), 127.23 (2aa '), 57.06 (d, J=7.3Hz, 2aa "), 54.03 (d, J=3.1Hz, 2aa’),31.30(2aa’),31.23(2aa”),28.05(2aa”),26.17(2aa’),26.10(2aa”),25.95 (2aa’),22.47(2aa’),22.45(2aa”),13.95(2aa’+2aa”).
HRMS(EI)m/z calculated for C13H17FNSCl[35][M]+273.0754,found 273.0752。
Embodiment 28
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- methylbenzylamine, obtained product such as structural formula Shown in (2-28), yield 83%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to N- methylbenzylamine, yield 98%. Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 82-84,2ab ': 2ab "=1:1 of product.1H NMR (400MHz,CDCl3) δ 7.29 (q, J=6.9Hz, 4H+4H, 2ab '+2ab "), 7.13 (d, J=7.0Hz, 1H+1H, 2ab '+ 2ab "), 4.90 (s, 2H, 2ab '), 4.60 (s, 2H, 2ab "), 3.18 (s, 3H, 2ab '), 2.98 (d, J=1.9Hz, 3H, 2ab”).19F NMR(376MHz,CDCl3)δ17.17(2ab’),13.23(2ab”).13C NMR(101MHz,CDCl3)δ 182.60 (d, J=320.5Hz), 181.30 (d, J=320.4Hz), 134.05 (d, J=3.3Hz), 129.09 (d, J= 15.5Hz), 128.54,128.52,128.06,127.64,58.78 (d, J=5.8Hz), 54.95 (d, J=5.6Hz), 41.00 (d, J=6.3Hz), 35.72 (d, J=6.9Hz) can not correspond at the peak in the carbon of nuclear magnetic resonance spectrum to 2ab ' and 2ab ", All peaks are listed.
HRMS(EI)m/z calculated for C9H10FNS[M]+183.0518,found 183.0517。
Embodiment 29
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- ethyl benzyl amine, obtained product such as structural formula Shown in (2-29), yield 86%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in Figure 85-87, product 2ac ': 2ac "=1:1.1H NMR(500MHz,CDCl3) δ 7.40-7.31 (m, 4H+4H, 2ac '+2ac "), 7.22 (d, J=7.1Hz, 1H + 1H, 2ac '+2ac "), 5.00 (s, 2H, 2ac '), 4.65 (s, 2H, 2ac "), 3.72 (q, J=7.2Hz, 2H, 2ac '), 3.46 (qd, J=7.2,1.9Hz, 2H, 2ac "), 1.25 (td, J=7.1,0.7Hz, 3H, 2ac '), 1.17 (t, J=7.2Hz, 3H, 2ac”).19F NMR(471MHz,CDCl3)δ15.01(2ac’),14.66(2ac”).13C NMR(126MHz,CDCl3)δ 182.81 (d, J=320.2Hz), 180.88 (d, J=321.6Hz), 134.46,134.43,129.08,128.94,128.42, 128.02,127.60,56.59 (d, J=5.5Hz), 52.27 (d, J=5.7Hz), 48.28 (d, J=6.2Hz), 44.08 (d, J =5.9Hz), 13.16,10.63. can not be corresponding to 2ac ' and 2ac " by the peak in the carbon of nuclear magnetic resonance spectrum, only by all peaks It lists.
HRMS(EI)m/z calculated for C10H12FNS[M]+197.0674,found 197.0672。
Embodiment 30
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N- Methylphenethylamine, obtained product such as structure Shown in formula (2-30), yield 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 88-90, product 2ad ': 2ad "=1:1.1H NMR(500MHz,CDCl3) δ 7.33 (dd, J=10.2,4.6Hz, 2H+2H, 2ad '+2ad "), 7.28-7.23 (m, 2H+2H, 2ad '+2ad "), 7.17 (d, J=7.0Hz, 1H+1H, 2ad '+2ad "), 3.93-3.88 (m, 2H, 2ad '), 3.74-3.68 (m, 2H, 2ad "), 3.20 (s, 3H, 2ad '), 3.08-3.03 (m, 2H, 2ad '), 3.01 (d, J= 2.3Hz, 3H, 2ad "), 2.92 (t, J=7.4Hz, 2H, 2ad ")19F NMR(471MHz,CDCl3)δ17.41(2ad’), 13.29(2ad’).19F NMR(471MHz,CDCl3)δ17.41(2ad’),13.29(2ad”).13C NMR(126MHz,CDCl3) δ 181.43 (d, J=319.9Hz), 181.39 (d, J=321.7Hz), 137.61,137.11,128.93,128.86, (128.81,128.70,127.14,126.91,57.27 d, J=5.9Hz), 53.54 (d, J=4.5Hz), 42.03 (d, J= 6.0Hz), 37.44 (d, J=6.5Hz), 34.53,31.65. the carbon of nuclear magnetic resonance can not be composed in peak it is corresponding to 2ad ' and 2ad " only lists all peaks.
HRMS(EI)m/z calculated for C10H12FNS[M]+197.0674,found 197.0671。
Embodiment 31
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to N-methylcyclohexylamine, obtained product such as structure Shown in formula (2-31), yield 85%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 91-93, product 2ae ': 2ae "=1:1.1H NMR(500MHz,CDCl3) δ 4.61 (ddd, J=11.2,7.8,4.1Hz, 1H, 2ae '), 4.15 (tt, J=12.0,3.7Hz, 1H, 2ae "), 3.23 (s, 3H, 2ae '), 3.00 (d, J=2.6Hz, 3H, 2ae "), 1.93-1.67 (m,5H+5H,2ae’+2ae”),1.54–1.28(m,4H+4H,2ae’+2ae”),1.18–1.05(m,1H+1H,2ae’+ 2ae”).19F NMR(471MHz,CDCl3)δ19.19(2ae’),11.90(2ae”).13C NMR(126MHz,CDCl3)δ 181.14 (d, J=319.4Hz), 181.05 (d, J=320.6Hz), 62.31 (d, J=7.4Hz), 59.06 (d, J= 6.3Hz), 35.80 (d, J=6.6Hz), 30.43 (d, J=8.0Hz), 30.31,28.72,25.37,25.31,25.22, 25.02. the peak in the carbon of nuclear magnetic resonance can not being composed is corresponding to 2ae ' and 2ae ", only lists all peaks.
HRMS(EI)m/z calculated for C8H14FNS[M]+175.0831,found 175.0833。
Embodiment 32
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to dibutyl amine, obtained product such as structural formula (2- 32) shown in, yield 84%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 94-96, product 2af.1H NMR(500MHz,CDCl3) δ 3.79-3.58 (m, 2H), 3.56-3.30 (m, 2H), 1.71 (dtd, J=9.5,7.7,5.9Hz, 2H), 1.61 (tt, J=9.0,7.6Hz, 2H), 1.45-1.30 (m, 4H), 1.03-0.91 (m, 6H)19F NMR(471MHz, CDCl3)δ14.82.13C NMR(126MHz,CDCl3) δ 181.33 (d, J=320.3Hz), 53.69 (d, J=6.0Hz), 49.77 (d, J=5.0Hz), 30.25,27.93,20.00,19.90,13.71,13.61.
HRMS(EI)m/z calculated for C9H18FNS[M]+191.1144,found 191.1143。
Embodiment 33
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to dihexylamine, obtained product such as structural formula (2- 33) shown in, yield 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra as shown in Figure 97-99, product 2ag.1H NMR(500MHz,CDCl3) δ 3.68-3.61 (m, 2H), 3.41 (td, J=7.8,1.4Hz, 2H), 1.79-1.68 (m, 2H), 1.65-1.59 (m, 2H), 1.33 (dd, J=14.5,10.2Hz, 12H), 0.94-0.86 (m, 6H)19F NMR(471MHz, CDCl3)δ14.78.13C NMR(126MHz,CDCl3) δ 181.31 (d, J=320.5Hz), 53.95 (d, J=5.9Hz), 50.04 (d, J=5.0Hz), 31.38,31.31,28.18,26.41,26.32,25.83,22.52,22.46,13.97, 13.94.
HRMS(EI)m/z calculated for C13H26FNS[M]+247.1770,found 247.1771。
Embodiment 34
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to diisopropylamine, obtained product such as structural formula (2- 34) shown in, yield 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 100-102, product 2ah.1H NMR(500MHz,CDCl3) δ 5.09 (d, J=5.6Hz, 1H), 3.72-3.54 (m, 1H), 1.39 (dd, J=6.9,2.5Hz, 6H), 1.27 (dd, J=6.8,0.8Hz, 6H)19F NMR(471MHz,CDCl3)δ22.39.13C NMR(126MHz,CDCl3)δ 182.69 (d, J=321.4Hz), 55.71 (d, J=6.0Hz), 49.15,21.61,21.57,18.90.
HRMS(EI)m/z calculated for C7H14FNS[M]+163.0831,found 163.0833。
Embodiment 35
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to dicyclohexylamine, obtained product such as structural formula Shown in (2-35), yield 85%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 103-105, product 2ai。1H NMR(500MHz,CDCl3)δ4.73(s,1H),3.16(s,1H),1.90(m,8H),1.73–1.65(m,4H), 1.48–1.21(m,8H).19F NMR(471MHz,CDCl3)δ22.72.13C NMR(126MHz,CDCl3) δ 182.76 (d, J= 323.6Hz),64.20,59.30,31.42,31.38,29.18,26.30,25.49,25.18,25.04.
HRMS(EI)m/z calculated for C13H22FNS[M]+243.1457,found 243.1456。
Embodiment 36
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to cyclopentamine, obtained product such as structural formula (2- 36) shown in, yield 78%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 106-108, product 2aj.1H NMR(500MHz,CDCl3) δ 3.60 (dt, J=20.3,6.4Hz, 4H), 1.96 (dd, J=8.9,5.3Hz, 4H)19F NMR (471MHz,CDCl3)δ19.90.13C NMR(126MHz,CDCl3) δ 178.67 (d, J=321.2Hz), 52.61 (d, J= 6.3Hz),48.93,25.72,24.60.
HRMS(EI)m/z calculated for C5H8FNS[M]+133.0361,found 133.0362。
Embodiment 37
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to cyclohexylamine, obtained product such as structural formula (2- 37) shown in, yield 81%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 109-111, product 2ak.1H NMR(400MHz,CDCl3)δ4.02–3.90(m,2H),3.74–3.61(m,2H),1.76–1.62(m,6H).19F NMR (376MHz,CDCl3)δ12.36.13C NMR(101MHz,CDCl3) δ 179.78 (d, J=319.7Hz), 52.10 (d, J= 6.5Hz), 47.72 (d, J=6.8Hz), 25.73,24.80,23.66.
HRMS(EI)m/z calculated for C6H10FNS[M]+147.0518,found 147.0517。
Embodiment 38
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to morpholine, obtained product such as structural formula (2-38) It is shown, yield 82%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 112-114, product 2al.1H NMR(500MHz,CDCl3)δ4.03–3.95(m,2H),3.84–3.79(m,2H),3.78–3.70(m,4H).19F NMR (471MHz,CDCl3)δ12.85.13C NMR(126MHz,CDCl3) δ 180.17 (d, J=320.1Hz), 65.77 (d, J= 1.5Hz), 50.45 (d, J=6.0Hz), 46.97 (d, J=5.0Hz)
HRMS(EI)m/z calculated for C5H8FNOS[M]+149.0311,found 149.0313。
Embodiment 39
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to thiomorpholine, obtained product such as structural formula (2- 39) shown in, yield 76%.Method 2 is identical as 1 method 2 of embodiment, and amine is only changed to thiomorpholine, yield 98%.Nuclear-magnetism Resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 115-117, product 2am.1H NMR(500MHz,CDCl3)δ 4.32–4.19(m,2H),4.05–3.95(m,2H),2.86–2.77(m,2H),2.76–2.67(m,2H).19F NMR (471MHz,CDCl3)δ14.44.13C NMR(126MHz,CDCl3) δ 180.07 (d, J=320.6Hz), 53.54 (d, J= 5.8Hz), 49.44 (d, J=5.9Hz), 27.65,26.61.
HRMS(EI)m/z calculated for C5H8FNS2[M]+165.0082,found 165.0080。
Embodiment 40
The present embodiment is identical as 1 method 1 of embodiment, and amine is only changed to piperazine, obtained product such as structural formula (2-40) It is shown.Yield is 88%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 118-120, product 2an ': 2an " =1:1.1H NMR(500MHz,DMSO)δ4.07(s,2H+2H,2an’+2an”),4.03–3.94(m,4H+4H,2an’+ 2an”),3.90(s,2H+2H,2an’+2an”).19F NMR(471MHz,DMSO)δ13.22(2an’),12.60(2an”).13C NMR (126MHz, DMSO) δ 179.69 (d, J=319.0Hz), 179.65 (d, J=319.1Hz), 48.95,48.90,48.54, 48.49,45.16,45.12,44.84,44.79. the peak in the carbon of nuclear magnetic resonance can not being composed is corresponding to 2an ' and 2an ", only will It lists at all peaks.
HRMS(EI)m/z calculated for C6H8F2N2S2[M]+210.0097,found 210.0095。
Embodiment 41
The present embodiment is identical as 1 method 2 of embodiment, and amine is only changed to totokaine, obtained product such as structural formula (2- 41) shown in, yield 89%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 121-123, product 2ao ': 2ao "=5:1.1H NMR(500MHz,CDCl3) δ 8.15 (dd, J=17.2,8.2Hz, 2H+2H, 2ao '+2ao "), 7.40 (d, J =7.6Hz, 1H, 2ao '), 7.28 (t, J=8.2Hz, 2H, 2ao "), 4.45 (t, J=5.8Hz, 2H+2H, 2ao '+2ao "), 4.13-4.03 (m, 2H, 2ao '), 3.83 (s, 2H, 2ao "), 2.72 (t, J=5.8Hz, 2H+2H, 2ao '+2ao "), 2.34 (s, 6H+6H, 2ao '+2ao "), 1.65 (dd, J=15.2,7.7Hz, 2H+2H, 2ao '+2ao "), 1.35 (dd, J=14.9, 7.4Hz, 2H+2H, 2ao '+2ao "), 0.91 (t, J=7.4Hz, 3H+3H, 2ao '+2ao ")19F NMR(471MHz,CDCl3)δ 25.27(2ao’),17.77(2ao”).13C NMR(126MHz,CDCl3) δ 182.05 (d, J=325.3Hz, 2ao '), 180.03 (d, J=320.6Hz, 2ao "), 165.35,146.53,143.45,131.35,131.08,130.38,127.08,125.89, (63.31,57.78,56.68 d, J=7.1Hz), 53.65,45.80,30.15,28.08,19.77,13.62,13.53. can not Peak in the carbon spectrum of nuclear magnetic resonance is corresponding to 2ao ' and 2ao ", only all peaks are listed.
HRMS(ESI)m/z calculated for C16H24FN2O2S[M+H+]+327.1537,found 327.1538.
Embodiment 42
The present embodiment is identical as 1 method 2 of embodiment, and amine is only changed to amoxapine, obtained product such as structural formula (2- 42) shown in, yield 89%.Nuclear magnetic resonance1H NMR、19F NMR、13C NMR spectra is as shown in Figure 124-126, product 2ap.1H NMR(500MHz,CDCl3) δ 7.43 (dd, J=8.6,2.3Hz, 1H), 7.31 (d, J=2.3Hz, 1H), 7.21 (d, J= 8.7Hz, 1H), 7.13 (dt, J=14.6,7.3Hz, 3H), 7.04 (t, J=7.5Hz, 1H), 4.10 (s, 2H), 3.85 (s, 2H), 3.64 (d, J=21.4Hz, 4H)19F NMR(471MHz,CDCl3)δ13.88.13C NMR(126MHz,CDCl3)δ 180.24 (d, J=320.6Hz), 159.43,158.18,151.70,139.46,133.15,130.64,128.67,127.18, (125.95,125.42,124.46,123.01,120.28,60.41,49.97 d, J=5.8Hz), 46.56 (d, J=9.6Hz), 46.11 (d, J=5.1Hz)
HRMS(ESI)m/z calculated for C18H16ClFN3OS[M+H+]+376.0681,found 376.0684。

Claims (7)

1. the thio acyl fluorides derivative of a kind of amine, which is characterized in that the derivative has formula:
Wherein,
R1For rubigan, o-methoxyphenyl, p-methylphenyl, p-bromophenyl, p-trifluoromethyl phenyl, p-fluorophenyl, adjacent fluorine Phenyl, 2- naphthalene, to acetylphenyl, para Toluic Acid's ethoxycarbonyl, phenyl, to N, N- (dimethylamino) ethylamino benzonitrile Perester radical, to N- aminomethyl phenyl, to N, N- 3,5-dimethylphenyl, cyclohexyl, benzyl, 3- thienyl, hexyl, butyl, isopropyl or 2- pyridyl group；
R2For methyl, ethyl, benzyl, hexyl, isopropyl, butyl, cyclohexyl or phenethyl；
Alternatively, R1-NH-R2For pyrrolidines, piperidines, morpholine, thiomorpholine, amoxapine, totokaine, piperazine or indoline.
2. the synthetic method of the thio acyl fluorides derivative of a kind of amine, which is characterized in that this method is with secondary amine, trifluoromethyl trimethyl Silane, sulphur and potassium fluoride are raw material, using organic solvent as solvent, after reacting at room temperature, obtain the amine sulphur as shown in formula (I) For acyl fluorides derivative:
The synthetic reaction is as shown in reaction formula (I):
Wherein,
R1For rubigan, o-methoxyphenyl, p-methylphenyl, p-bromophenyl, p-trifluoromethyl phenyl, p-fluorophenyl, adjacent fluorine Phenyl, 2- naphthalene, to acetylphenyl, para Toluic Acid's ethoxycarbonyl, phenyl, to N, N- (dimethylamino) ethylamino benzonitrile Perester radical, to N- aminomethyl phenyl, to N, N- 3,5-dimethylphenyl, cyclohexyl, benzyl, 3- thienyl, hexyl, butyl, isopropyl or 2- pyridyl group；
R2For methyl, ethyl, benzyl, hexyl, isopropyl, butyl, cyclohexyl or phenethyl；
Alternatively, R1-NH-R2For pyrrolidines, piperidines, morpholine, thiomorpholine, amoxapine, totokaine, piperazine or indoline；
Specific synthesis process: first by the secondary amine, potassium fluoride, sulphur, be under nitrogen protection added in the organic solvent, with After trifluoromethyl trimethylsilane is added, at room temperature, react 1-12 hour, react obtain the thio acyl fluorides of amine shown in formula (I) Derivative；
The molar ratio of the raw material is secondary amine: trifluoromethyl trimethylsilane: sulphur: potassium fluoride=1: 5-10: 4-8: 3-6.
3. synthetic method according to claim 2, which is characterized in that the organic solvent be n,N-Dimethylformamide or Tetrahydrofuran.
4. the synthetic method of the thio acyl fluorides derivative of a kind of amine, which is characterized in that this method is with secondary amine, fluoroform sulphur silver and bromine Change potassium is raw material, using organic solvent as solvent, after reacting at room temperature, is obtained such as the thio acyl fluorides derivative of amine shown in formula (I):
The synthetic reaction is as shown in reaction formula (II):
Wherein,
R1For phenyl, m-methoxyphenyl, 2- naphthalene, chlorphenyl, Chloro-O-Phenyl, o-bromophenyl, p-trifluoromethyl phenyl, right Nitrobenzophenone, to cyano-phenyl, to acetylphenyl, 2- pyridyl group, 3- thienyl, benzyl or to N, N- (dimethylamino) second Yl benzoic acid ester group；
R2For methyl or butyl；
Alternatively, R1-NH-R2For amoxapine, thiomorpholine or totokaine；
Specific synthesis process: first the secondary amine, fluoroform sulphur silver and potassium bromide are dissolved in organic solvent, at room temperature instead It answers, it is derivative to obtain the thio acyl fluorides of amine shown in formula (I)；
The molar ratio of the raw material is secondary amine: fluoroform sulphur silver: potassium bromide=1: 1.5-3: 1.5-3.
5. synthetic method according to claim 4, which is characterized in that the organic solvent is acetonitrile, methylene chloride, N, N- Dimethylformamide, tetrahydrofuran, dimethyl sulfoxide, toluene, Isosorbide-5-Nitrae dioxane or 1,2- dichloroethanes.
6. synthetic method according to claim 2 or 4, which is characterized in that further, the amine sulphur that reaction is obtained It is isolated and purified for acyl fluorides derivative.
7. synthetic method according to claim 6, which is characterized in that described isolate and purify be with volume ratio is ethyl acetate : the solution of petroleum ether 1: 100~10 carries out column chromatography.
CN201910034306.1A 2019-01-15 2019-01-15 Amine thioacyl fluoride derivatives and synthetic method thereof Active CN109836365B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910034306.1A CN109836365B (en) 2019-01-15 2019-01-15 Amine thioacyl fluoride derivatives and synthetic method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910034306.1A CN109836365B (en) 2019-01-15 2019-01-15 Amine thioacyl fluoride derivatives and synthetic method thereof

Publications (2)

Publication Number Publication Date
CN109836365A true CN109836365A (en) 2019-06-04
CN109836365B CN109836365B (en) 2021-02-26

Family

ID=66883793

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910034306.1A Active CN109836365B (en) 2019-01-15 2019-01-15 Amine thioacyl fluoride derivatives and synthetic method thereof

Country Status (1)

Country Link
CN (1) CN109836365B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111056889A (en) * 2019-11-22 2020-04-24 华东师范大学 N-alkyl/N-aryl thioamide derivatives and synthesis method and application thereof
CN111100058A (en) * 2019-11-22 2020-05-05 华东师范大学 3, 3-dicarboxylic ester-indoline-2-thioketone compound and synthesis method and application thereof
CN115925598A (en) * 2022-12-05 2023-04-07 领海科技(青岛)有限公司 Synthetic method of thiofluorocarboxylic acid amide

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111056889A (en) * 2019-11-22 2020-04-24 华东师范大学 N-alkyl/N-aryl thioamide derivatives and synthesis method and application thereof
CN111100058A (en) * 2019-11-22 2020-05-05 华东师范大学 3, 3-dicarboxylic ester-indoline-2-thioketone compound and synthesis method and application thereof
CN111056889B (en) * 2019-11-22 2022-01-11 华东师范大学 N-alkyl/N-aryl thioamide derivatives and synthesis method and application thereof
CN115925598A (en) * 2022-12-05 2023-04-07 领海科技(青岛)有限公司 Synthetic method of thiofluorocarboxylic acid amide
CN115925598B (en) * 2022-12-05 2024-04-12 史大永 Synthesis method of thiofluoro-formic acid amide

Also Published As

Publication number Publication date
CN109836365B (en) 2021-02-26

Similar Documents

Publication Publication Date Title
CN109836365A (en) The thio acyl fluorides derivative of a kind of amine and its synthetic method
Matos et al. Synthetic approaches and applications of sulfonimidates
CN111423394B (en) Synthesis method of 1,3, 4-oxadiazole heterocyclic compound
Sohrabnezhad et al. High yielding protocol for direct conversion of thiols to sulfonyl chlorides and sulfonamides
CN104447604B (en) A kind of synthetic method of chirality quaternary carbon oxazoline ketonic compound
Sá et al. Synthesis of allylic thiocyanates and novel 1, 3-thiazin-4-ones from 2-(bromomethyl) alkenoates and S-nucleophiles in aqueous medium
CN113912577B (en) Rockwell intermediate, rockwell and its derivative, and preparation and application
EP3207023B1 (en) Process for the preparation of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone and derivatives thereof
EP3207024B1 (en) Process for the preparation of halo-substituted trifluoroacetophenones
CN107383097B (en) The preparation method of the phosphonylation derivative of N- phenyl -3- benzylidene iso-indoles -1- ketone
CN105175375B (en) The method that the acetylenic ketone protected using acetoxyl group prepares Benzofurantone compound
CN112898217B (en) Trifluoromethyl oxazolone compound, preparation method thereof and application thereof in anti-cancer drugs
Li et al. Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid
CN113444101A (en) Cyclopentane chromanone spliced bis-spiro-indene dione oxoindole compound and preparation method and application thereof
CN112125891B (en) N2Selective tetrahydrofuran/tetrahydrothiophene substituted triazole derivative and synthesis method and application thereof
CN112876507B (en) Trisubstituted olefin tertiary phosphine compound and preparation method thereof
JP4509327B2 (en) Process for producing N, N-disubstituted-4-aminocrotonic acid ester
CN111170944A (en) 3-azabicyclo [6.2.0] compounds, and synthetic method and application thereof
JP5943387B2 (en) Novel triflon derivative and method for producing the same
KR20090085173A (en) New alkyl aryl selenide derivatives and process for preparing thereof
JP2022104572A (en) Process for producing 1,3-diaryl-substituted tetrazolone inner salt
Požgan et al. A New Synthetic Route Towards Aliskiren Intermediates
KR100701743B1 (en) Novel Making Proces of the Bambuterol
Shao et al. College of Chemistry and Molecular Engineering, Zhengzhou University, No. 75, Daxue Road, Zhengzhou City, Henan Province 450052, PR China
CN110903243A (en) 1, 2-dihydro-3H-cyclopenta [ b ] quinoline-3-ketone compound and preparation method and application thereof

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