CN108997243A - A method of synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound - Google Patents

A method of synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound Download PDF

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CN108997243A
CN108997243A CN201810736206.9A CN201810736206A CN108997243A CN 108997243 A CN108997243 A CN 108997243A CN 201810736206 A CN201810736206 A CN 201810736206A CN 108997243 A CN108997243 A CN 108997243A
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sulfydryl
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class compound
difluoromethyl
difluoromethyl benzo
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CN108997243B (en
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翁志强
李正宇
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Fuzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/60—Naphthoxazoles; Hydrogenated naphthoxazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/62—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems having two or more ring systems containing condensed 1,3-oxazole rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Abstract

The invention discloses a kind of methods for synthesizing 2- sulfydryl -3- difluoromethyl benzo oxazole class compound: using chlorine difluoroacetic acid sodium, sulphur powder as reactant, using O-aminophenol derivatives as substrate, under alkaline condition, in a solvent, it is heated to 50-120 DEG C, 2-12h is stirred, after reaction, reaction solution obtains 2- sulfydryl -3- difluoromethyl benzo oxazoline compound after processing.The advantages that generally higher, raw material is easy to get synthetic method of the invention with yield, easy to operate, and substrate is wide, has good prospects for commercial application.

Description

A method of synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound
Technical field
The invention belongs to organic fluorine chemistries to synthesize field, and in particular to a kind of synthesis 2- sulfydryl -3- difluoromethyl benzo evil The method of azole compounds.
Background technique
Organic fluoride-containing compound has special physics, chemical property, and it is more to be used for medicine, pesticide and functional material etc. A scientific domain.Fluoro-containing group is introduced into organic molecule, tends to the lipophilicity, metabolic stability and the drop that improve compound Low molecular surface tension etc..Wherein, difluoromethyl group is considered as the equal polar bodys and isostere of hydroxyl, is introduced into It is a kind of effective means that its bioactivity is transformed into organic molecule.
On the other hand, 2- mercaptobenzoxazole class compound is a kind of important heterocyclic compound, and being widely present in has In bioactive molecule and drug molecule, the bioactivity of multiplicity, such as antibiotic property are shown, also can be used as heart protective agent (anti-ischemic medicine), macrophage migration inhibition factor (MIF) antagonist, the inhibitor of streptococcus hyaluronate lyase.Two Fluoromethyl group is introduced on 2- mercaptobenzoxazole class compound, may assign compound new bioactivity.
The present invention utilize some raw materials simple and easy to get, one-step synthesis 2- sulfydryl -3- difluoromethyl benzo oxazoline compound, It is expected to be applied on medicine, pesticide and functional material.
Summary of the invention
In view of the above-mentioned deficiencies in the prior art, it is an object of the present invention to provide a kind of synthesis 2- sulfydryl -3- difluoromethyl benzo The method for disliking azole compounds, difluoromethyl group is introduced on 2- mercaptobenzoxazole class compound；Synthetic method tool There is the advantages that yield is high, raw material is easy to get, easy to operate, substrate is wide, there is good prospects for commercial application.
To achieve the above object, the present invention adopts the following technical scheme:
A method of synthesis 2- sulfydryl -3- difluoromethyl benzo oxazoline compound is reaction with chlorine difluoroacetic acid sodium, sulphur powder Object, using O-aminophenol derivatives as substrate, under alkaline condition, heated reaction obtains the 2- sulfydryl -3- in a solvent Difluoromethyl benzo oxazoline compound；
Its reaction equation are as follows:；
Its specific reaction step are as follows: in nitrogen atmosphere, to magnetic stirring apparatus container in be added chlorine difluoroacetic acid sodium, Sulphur powder, O-aminophenol derivatives, alkali, molecular sieve, solvent shut plug after mixing, be heated to 50-120 DEG C it is (excellent It is selected as 70 DEG C), being stirred to react 2-12h(is preferably 3h) after, it is post-treated to obtain 2- sulfydryl -3- difluoromethyl benzo oxazole class Close object.
The post-processing are as follows: reaction solution is extracted with ethyl acetate 3 times, merges organic phase, adds saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent, and obtained crude product is elution with pentane and ethyl acetate Agent, through the isolated 2- sulfydryl -3- difluoromethyl benzo oxazole class compound of silica gel column chromatography.
In synthetic method of the invention, chlorine difluoroacetic acid sodium, sulphur powder, O-aminophenol derivatives, alkali and solvent Molar ratio is 0.10-5.00:0.10-5.00:0.1-1.00:0.2-4:5-50.
The alkali is sodium tert-butoxide or sodium hydroxide.
The solvent is n,N-Dimethylformamide.
The O-aminophenol derivatives structure general formula are as follows:, it is specially appointing in following formula 1- formula 22 It anticipates one kind:
。
The general structure of obtained 2- sulfydryl -3- difluoromethyl benzo oxazoline compound are as follows:, It is specially any one in following formula 1- formula 22:
。
The beneficial effects of the present invention are:
The present invention with chlorine difluoroacetic acid sodium cheap and easy to get, sulphur powder, O-aminophenol derivatives etc. for raw material, one-step synthesis 2- mercapto Base -3- difluoromethyl benzo oxazole class compound, easy to operate, universal yield with higher, and substrate spectrum is wide, has Good prospects for commercial application.
Detailed description of the invention
Fig. 1 is the bromo- benzoxazoles mono-crystalline structures schematic diagram of 2- sulfydryl -3- difluoromethyl -5- made from embodiment 1.
Specific embodiment
In order to make content of the present invention easily facilitate understanding, With reference to embodiment to of the present invention Technical solution is described further, but the present invention is not limited only to this.
Embodiment 1
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, is added 0.4 mmol 2- amino-4-bromophenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl formyl Amine after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated bromo- benzoxazoles of 2- sulfydryl -3- difluoromethyl -5- (yield 90%) of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.69 (t, J = 58.3 Hz, 1H), 7.63 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.8 (d, J = 58.2 Hz). 13C NMR (101 MHz, CDCl3) δ 178.6 (t, J = 3.5 Hz), 145.6 (s), 128.7 (s), 128.3 (t, J = 1.5 Hz), 118.6 (s), 114.5 (t, J = 2.9 Hz), 111.9 (s), 110.7 (t, J = 252.4 Hz). GC-MS m/z 279 (M+).
Embodiment 2
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, is added 0.4 mmol 2- amino -5- chlorophenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl formyl Amine after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated chloro- benzoxazoles of 2- sulfydryl -3- difluoromethyl -6- (yield 78%) of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.70 (t, J = 58.3 Hz, 1H), 7.41 (s, 1H), 7.40 (d, J = 10.8 Hz, 1H), 7.35 (d, J = 8.5 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.8 (d, J = 58.3 Hz). 13C NMR (101 MHz, CDCl3) δ 178.6 (t, J = 3.5 Hz), 146.9(s), 131.7 (s), 125.9 (s), 125.9 (t, J = 1.5 Hz), 111.8 (t, J = 2.7 Hz), 111.5(s), 110.8 (t, J = 252.1 Hz). GC-MS m/z 235 (M+).
Embodiment 3
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 2- Amino-4-nitrophenol is added, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl methyl Amide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium-chloride molten Liquid washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is to wash with pentane and ethyl acetate De- agent, passes through the isolated 2- sulfydryl -3- difluoromethyl -5- nitro of silica gel column chromatography-benzoxazoles (yield 65%).
1H NMR (400 MHz, CDCl3) δ 8.35 (s, 2H), 7.72 (t, J = 58.1 Hz, 1H), 7.53 (d, J = 9.5 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.6 (d, J = 58.1 Hz).13C NMR (101 MHz, CDCl3) δ 178.6 (t, J = 3.3 Hz), 150.1 (s), 145.6 (s), 127.9 (t, J = 1.4 Hz),, 122.0 (s), 110.8 (s), 110.7 (t, J = 253.4 Hz),107.3 (t, J = 3.0 Hz). GC-MS m/z 246 (M+).
Embodiment 4
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 4- amino-3-hydroxy first is added Sour methyl esters, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,N- Dimethylformamide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturation Sodium chloride solution washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane and acetic acid Ethyl ester is eluant, eluent, passes through the isolated 2- sulfydryl -3- difluoromethyl -6- ester group-benzoxazoles (yield of silica gel column chromatography 75%).
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.3 Hz, 1H), 8.01 (s, 1H), 7.72 (t, J = 58.2 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H), 3.98 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -103.9 (d, J = 58.2 Hz). 13C NMR (101 MHz, CDCl3) δ 179.1 (t, J = 3.2 Hz), 165.4 (s), 146.4 (s), 130.6 (t, J = 1.4 Hz), 128.0 (s), 127.7 (s), 111.8 (s), 110.9 (t, J = 2.7 Hz), 110.8 (t, J = 252.5 Hz), 52.7 (s). GC-MS m/ z 259 (M+).
Embodiment 5
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 2- Amino-5-nitrophenol is added, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl methyl Amide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium-chloride molten Liquid washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is to wash with pentane and ethyl acetate De- agent, passes through the isolated 2- sulfydryl -3- difluoromethyl -6- nitro of silica gel column chromatography-benzoxazoles (yield 69%).
1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.8 Hz, 1H), 8.27 (s, 1H), 7.73 (t, 1H), 7.61 (d, J = 8.7 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.7 (d, J = 58.1 Hz). 13C NMR (101 MHz, CDCl3) δ 178.8 (t, J = 3.2 Hz), 146.2 (s), 145.56 (s), 132.1 (t, J = 1.6 Hz), 122.0 (s), 111.0 (t, J = 2.9 Hz), 110.7 (t, J = 253.7 Hz), 106.8 (s). GC-MS m/z 246 (M+).
Embodiment 6
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, is added 0.4 mmol 2- amino -6- bromophenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl formyl Amine after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated bromo- benzoxazoles of 2- sulfydryl -3- difluoromethyl -7- (yield 84%) of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.70 (t, J = 58.2 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.25 (t, J = 8.1 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.9 (d, J = 58.2 Hz). 13C NMR (101 MHz, CDCl3) δ 178.0 (t, J = 3.5 Hz), 144.8 (s), 128.8(s), 128.0 (t, J = 1.5 Hz), 126.8 (s), 110.9 (t, J = 252.4 Hz), 110.2 (t, J = 2.7 Hz), 103.0 (s). GC-MS m/z 279 (M+).
Embodiment 7
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 4, the chloro- 2- aminobenzene of 6- bis- is added Phenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDiformazan Base formamide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturation chlorination Sodium solution washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane and ethyl acetate For eluant, eluent, pass through the isolated bis- chloro- benzoxazoles (yield 52%) of 2- sulfydryl -3- difluoromethyl -5,7- of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.66 (t, J = 58.1 Hz, 1H), 7.37 (s, 1H), 7.36 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -103.9 (d, J = 58.1 Hz). 13C NMR (101 MHz, CDCl3) δ 177.9 (t, J = 3.4 Hz), 142.0 (s), 132.0 (s), 128.8 (t, J = 1.5 Hz), 125.9 (s), 116.7 (s), 110.7 (t, J = 253.2 Hz), 110.1 (t, J = 2.9 Hz). GC-MS m/z 271 (M+).
Embodiment 8
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 2- amino -4- methylphenol is added, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl methyl Amide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium-chloride molten Liquid washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is to wash with pentane and ethyl acetate De- agent, passes through the isolated 2- sulfydryl -3- difluoromethyl -5- methyl of silica gel column chromatography-benzoxazoles (yield 65%).
1H NMR (400 MHz, CDCl3) δ 7.72 (t, J = 58.4 Hz, 1H), 7.28 (s, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 2.47 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -104.1 (d, J = 58.4 Hz). 13C NMR (101 MHz, CDCl3) δ 179.1 (t, J = 3.7 Hz), 144.9 (s), 136.10 (s), 127.1 (t, J = 1.6 Hz), 126.3 (s), 111.7 (t,J = 2.5 Hz), 110.9 (t, J = 251.3 Hz), 110.2 (s), 21.5 (s). GC-MS m/z 215 (M+).
Embodiment 9
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, is added 0.4 mmol 2- amino-4-fluorophenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl formyl Amine after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated fluoro- benzoxazoles of 2- sulfydryl -3- difluoromethyl -5- (yield 84%) of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.70 (t, J = 58.3 Hz, 1H), 7.34 (dd, J = 8.9, 4.0 Hz, 1H), 7.21 (d, J = 7.4 Hz, 1H), 7.07 (t, J = 9.0 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -104.1 (d, J = 58.3 Hz), -113.7 – -114.5 (m). 13C NMR (101 MHz, CDCl3) δ 179.3 (t, J = 3.5 Hz), 160.3 (d, J = 245.8 Hz), 142.7 (d, J = 2.1 Hz), 127.7 (dt, J = 3.0, 1.3 Hz), 112.5 (d, J = 25.3 Hz), 111.3 (d, J = 9.6 Hz), 110.7 (t, J = 252.2 Hz), 99.8 (dt, J = 30.3, 2.7 Hz). GC-MS m/z 219 (M+).
Embodiment 10
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, is added 0.4 mmol 2- amino -4- chlorophenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDimethyl formyl Amine after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated chloro- benzoxazoles of 2- sulfydryl -3- difluoromethyl -5- (yield 82%) of silica gel column chromatography.
1H NMR (400 MHz, CDCl3) δ 7.69 (t, J = 58.3 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J = 10.4 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -103.9 (d, J = 58.2 Hz). 13C NMR (101 MHz, CDCl3) δ 178.8 (t, J = 3.5 Hz), 145.2 (s), 131.6 (s), 128.0 (t, J = 1.5 Hz), 125.8 (s), 111.7 (t, J = 2.9 Hz), 111.4(s), 110.7(t, J = 252.3 Hz). GC-MS m/z 235 (M+).
Embodiment 11
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 2- amino-4-methoxyl benzene is added Phenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDiformazan Base formamide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturation chlorination Sodium solution washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane and ethyl acetate For eluant, eluent, pass through the isolated 2- sulfydryl -3- difluoromethyl -5- methoxyl group of silica gel column chromatography-benzoxazoles (yield 50%).
1H NMR (400 MHz, CDCl3) δ 7.73 (t, J = 58.4 Hz, 1H), 7.27 (d, J = 9.1 Hz, 1H), 6.99 (s, 1H), 6.88 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -104.2 (d, J = 58.4 Hz). 13C NMR (101 MHz, CDCl3) δ 179.4 (t, J = 3.6 Hz), 158.0 (s), 140.9 (s), 127.8 (t, J = 1.4 Hz), 111.70 (s), 111.0(s), 110.9 (t, J = 251.5 Hz), 97.1 (t, J = 2.7 Hz), 56.2 (s). GC-MS m/z 231 (M+).
Embodiment 12
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol 4- amino-3-hydroxy first is added Acid, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,NDiformazan Base formamide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturation chlorination Sodium solution washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane and ethyl acetate For eluant, eluent, pass through the isolated 2- sulfydryl -3- difluoromethyl -6- carboxyl of silica gel column chromatography-benzoxazoles (yield 67%).
Embodiment 13
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 chloro- 6 nitro of mmol 2- amino -4- is added Phenol, 2 mmol S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium tert-butoxides, 60 mg molecular sieves and 6 mLN,N- two Methylformamide after being stirred to react 3 h in 70 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturation chlorine Change sodium solution washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane and acetic acid second Ester is eluant, eluent, passes through the chloro- 7- nitro-benzoxazoles (yield of the isolated 2- sulfydryl -3- difluoromethyl -5- of silica gel column chromatography 29%).
Embodiment 14
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 0.4 mmol Ortho-Aminophenol, 2 mmol are added S8, 2 mmol difluoro sodium chloroacetates, 1.6 mmol sodium hydroxides, 15 % mol sodium metaperiodates and 6 mLN,NDimethyl formyl Amine after being stirred to react 5 h in 80 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution Washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane and ethyl acetate Agent passes through the isolated 2- sulfydryl -3- difluoromethyl of silica gel column chromatography-benzoxazoles (yield 80%).
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with Modification, is all covered by the present invention.

Claims (7)

1. a kind of method for synthesizing 2- sulfydryl -3- difluoromethyl benzo oxazole class compound, it is characterised in that: with chlorine difluoroacetic acid Sodium, sulphur powder are reactant, and using O-aminophenol derivatives as substrate, under alkaline condition, heated reaction is made in a solvent 2- sulfydryl -3- difluoromethyl benzo oxazole class compound；The knot of the 2- sulfydryl -3- difluoromethyl benzo oxazole class compound Structure formula are as follows:。
2. the method for synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound according to claim 1, feature exist In: the solvent is n,N-Dimethylformamide.
3. the method for synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound according to claim 1, feature exist In the molar ratio of: chlorine difluoroacetic acid sodium used, sulphur powder, O-aminophenol derivatives, alkali and solvent be 0.10-5.00:0.10- 5.00:0.1-1.00:0.2-4:5-50。
4. the method for synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound according to claim 1, feature exist In: the alkali is sodium tert-butoxide or sodium hydroxide.
5. the method for synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound according to claim 1, feature exist In: the temperature for heating reaction is 50-120 DEG C, reaction time 2-12h.
6. the method for synthesis 2- sulfydryl -3- difluoromethyl benzo oxazole class compound according to claim 1, feature exist In: the structural formula of the O-aminophenol derivatives is；It is specially any one in following formula 1- formula 22 Kind:
。
7. a kind of 2- sulfydryl -3- difluoromethyl benzo oxazole class chemical combination of as the method according to claim 1 to 6 synthesis Object, it is characterised in that: it is specially any one in following formula 1- formula 22:
。
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CN115960055B (en) * 2022-05-20 2024-05-10 华南农业大学 N-difluoromethyl benzothiazole/oxazolselenone compound, and preparation method and application thereof

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