CN103102321A - Method for preparing 2-substituted benzoxazole compound - Google Patents
Method for preparing 2-substituted benzoxazole compound Download PDFInfo
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- CN103102321A CN103102321A CN2013100259844A CN201310025984A CN103102321A CN 103102321 A CN103102321 A CN 103102321A CN 2013100259844 A CN2013100259844 A CN 2013100259844A CN 201310025984 A CN201310025984 A CN 201310025984A CN 103102321 A CN103102321 A CN 103102321A
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- azole compounds
- benzo azole
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- 238000000034 method Methods 0.000 title claims abstract description 43
- -1 2-substituted benzoxazole compound Chemical class 0.000 title claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 107
- 239000002994 raw material Substances 0.000 claims abstract description 67
- 239000002904 solvent Substances 0.000 claims abstract description 42
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003054 catalyst Substances 0.000 claims abstract description 31
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims abstract description 23
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 claims abstract description 19
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 16
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 claims abstract description 14
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 229910052751 metal Inorganic materials 0.000 claims abstract description 10
- 239000002184 metal Substances 0.000 claims abstract description 10
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 10
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 6
- 150000003935 benzaldehydes Chemical class 0.000 claims abstract description 3
- 150000003939 benzylamines Chemical class 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 84
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 75
- 239000000047 product Substances 0.000 claims description 52
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 40
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 28
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 27
- 239000012074 organic phase Substances 0.000 claims description 26
- 230000035484 reaction time Effects 0.000 claims description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 15
- 238000005406 washing Methods 0.000 claims description 14
- RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 7
- 235000011152 sodium sulphate Nutrition 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 229960004217 benzyl alcohol Drugs 0.000 claims description 6
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- JVJQPDTXIALXOG-UHFFFAOYSA-N nitryl fluoride Chemical compound [O-][N+](F)=O JVJQPDTXIALXOG-UHFFFAOYSA-N 0.000 claims description 2
- 238000002156 mixing Methods 0.000 abstract description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 abstract description 4
- 238000000605 extraction Methods 0.000 abstract 1
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 238000001819 mass spectrum Methods 0.000 description 39
- 230000005311 nuclear magnetism Effects 0.000 description 39
- XBHOUXSGHYZCNH-UHFFFAOYSA-N 2-phenyl-1,3-benzothiazole Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2S1 XBHOUXSGHYZCNH-UHFFFAOYSA-N 0.000 description 12
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 11
- POSRBSJJCMKQNU-UHFFFAOYSA-N 1-methyl-2-phenylbenzimidazole Chemical compound N=1C2=CC=CC=C2N(C)C=1C1=CC=CC=C1 POSRBSJJCMKQNU-UHFFFAOYSA-N 0.000 description 10
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 8
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 8
- FIISKTXZUZBTRC-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2O1 FIISKTXZUZBTRC-UHFFFAOYSA-N 0.000 description 7
- XTFNBGUXOKGTDK-UHFFFAOYSA-N [4-(1,3-benzoxazol-2-yl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1C1=NC2=CC=CC=C2O1 XTFNBGUXOKGTDK-UHFFFAOYSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- KETHPFOJWJUQFI-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-benzoxazole Chemical compound C1=CC(F)=CC=C1C1=NC2=CC=CC=C2O1 KETHPFOJWJUQFI-UHFFFAOYSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- ZNBHIZVPIRZVLA-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-1,3-benzoxazole Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC2=CC=CC=C2O1 ZNBHIZVPIRZVLA-UHFFFAOYSA-N 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- CJAAPVQEZPAQNI-UHFFFAOYSA-N (2-methylphenyl)methanamine Chemical compound CC1=CC=CC=C1CN CJAAPVQEZPAQNI-UHFFFAOYSA-N 0.000 description 1
- CIUYJYRQKYGNQP-UHFFFAOYSA-N (3-nitrophenyl)methanamine Chemical compound NCC1=CC=CC([N+]([O-])=O)=C1 CIUYJYRQKYGNQP-UHFFFAOYSA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- MPWSRGAWRAYBJK-UHFFFAOYSA-N (4-tert-butylphenyl)methanamine Chemical compound CC(C)(C)C1=CC=C(CN)C=C1 MPWSRGAWRAYBJK-UHFFFAOYSA-N 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- 150000000183 1,3-benzoxazoles Chemical class 0.000 description 1
- QNYLRZBOTOWMAE-UHFFFAOYSA-N 2-(3-nitrophenyl)-1,3-benzothiazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2SC3=CC=CC=C3N=2)=C1 QNYLRZBOTOWMAE-UHFFFAOYSA-N 0.000 description 1
- KEJBDGQLLLLBGE-UHFFFAOYSA-N 2-(4-nitrophenyl)-1,3-benzothiazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NC2=CC=CC=C2S1 KEJBDGQLLLLBGE-UHFFFAOYSA-N 0.000 description 1
- RBKGJKUWWDNBNT-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-1,3-benzothiazole Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC2=CC=CC=C2S1 RBKGJKUWWDNBNT-UHFFFAOYSA-N 0.000 description 1
- BBEDRGWUDRUNQC-UHFFFAOYSA-N 2-[bis(4-fluorophenyl)methoxy]ethanamine Chemical compound C=1C=C(F)C=CC=1C(OCCN)C1=CC=C(F)C=C1 BBEDRGWUDRUNQC-UHFFFAOYSA-N 0.000 description 1
- BCSVCWVQNOXFGL-UHFFFAOYSA-N 3,4-dihydro-4-oxo-3-((5-trifluoromethyl-2-benzothiazolyl)methyl)-1-phthalazine acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 BCSVCWVQNOXFGL-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950004385 flunamine Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229950005346 zopolrestat Drugs 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
本发明制备2-取代苯并唑类化合物的方法，采用苄胺类化合物或苯甲醛类化合物或苯甲醇类化合物，以及邻苯胺——N-甲基邻苯二胺、邻氨基苯酚、邻氨基苯硫酚为原料，采用金属钯、铂或钌为催化剂，以N，N-二甲基甲酰胺、N，N-二甲基乙酰胺或N-甲基吡咯烷酮为溶剂，其制备步骤包括：⑴原料混合；⑵反应；⑶分离和萃取；⑷干燥和浓缩。在整个制备过程中，无需使用氧化剂和氢接受体，而且使用的部分催化剂可回收循环使用。本发明的方法原子经济性高，后处理简单，反应条件温和，具有一定的工业应用前景。The method for preparing 2-substituted benzoxazole compounds in the present invention adopts benzylamine compounds or benzaldehyde compounds or benzyl alcohol compounds, and o-aniline——N-methyl o-phenylenediamine, o-aminophenol, o-amino Thiophenol is used as a raw material, metal palladium, platinum or ruthenium is used as a catalyst, and N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone is used as a solvent. The preparation steps include: ⑴Raw material mixing; ⑵reaction; ⑶separation and extraction; ⑷drying and concentration. In the whole preparation process, no oxidizing agent and hydrogen acceptor are used, and part of the catalyst used can be recovered and recycled. The method of the invention has high atom economy, simple post-treatment, mild reaction conditions, and has certain industrial application prospects.
Description
Technical field
The present invention relates to the synthetic method at the benzazoles compound of the field widespread uses such as medicine, agricultural chemicals, chemical industry, specifically, is a kind of method that 2-of preparation replaces the benzo azole compounds.
Technical background
Benzazoles compound (benzoxazoles, benzothiazole, benzoglyoxaline) is a very important heterogeneous ring compound of class, modification to the benzazoles derivative is mainly to introduce different groups on phenyl ring, or introduce different active groups, wherein 2 bit substituents having the greatest impact to its activity on 2.2-replaces the benzo azole compounds and derivative has utilization extremely widely in fields such as medicine, agricultural chemicals, chemical industry, materials: (as shown in the formula) A is the antihypertensive drug telmisartan; B is the medicine zopolrestat for the treatment of diabetes; C is the compound with HIV (human immunodeficiency virus)-resistant activity;
It is take O-Phenylene Diamine (Ortho-Aminophenol, near amino thiophenols) compounds and carboxylic acid and derivative (acyl chlorides, acid amides, ester, nitrile etc.) thereof as raw material that 2-replaces the traditional preparation method of benzo azole compounds, synthesizes benzazoles compound (Hein, D.
J. Am. Chem. Soc., 1996, (79): 427-429).Although this method raw material sources are wide, yield is higher, and reaction conditions is comparatively harsh, need with high temperature, strong acid treatment, and long reaction time, the generation of " three wastes " is large, and is unfavorable to environment.In recent years, preparing 2-with aldehydes and alcohol compound as reaction raw materials replaces the benzo azole compounds and becomes gradually study hotspot in industry, be characterized in: reaction conditions is relatively gentle, raw material is than carboxylic acid, acyl chlorides low toxicity more, but, (pertinent literature is seen: Bahrami, K. still to need to use stoichiometric oxygenant oxidation to be closed into the benzazoles compound
J. Org. Chem., 2008, (73): 6835 – 6837; Blacker, A. J.
Org. Lett., 2009, (11): 2039-2042; US Patent No. 2003148387A1; Chinese patent CN101481355A; Chinese patent CN101235017A).By product is introduced in the use meeting of described oxygenant in reaction system, be unfavorable for aftertreatment, and can bring certain trouble to the purifying of product, and can produce the disadvantageous by product of environment.The method for preparing 2-replacement benzo azole compounds under the condition of non-oxidation agent and Hydrogen acceptor there is not yet bibliographical information so far.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, provide a kind of 2-of preparation to replace the method for benzo azole compounds, it need not to use oxygenant and Hydrogen acceptor, catalyzer is recyclable to be recycled, Atom economy is high, aftertreatment is simple, and reaction conditions is gentle, has certain prospects for commercial application.
For realizing above goal of the invention, the present invention has taked following technical scheme.
A kind of method for preparing 2-replacement benzo azole compounds is characterized in that, comprises the following steps:
(1) raw material mixes
adopt benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds, and adjacent aniline is raw material, adopt palladium metal, platinum or ruthenium are catalyzer, with N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA) or N-Methyl pyrrolidone are solvent, add benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds successively in there-necked flask, and adjacent aniline, catalysts and solvents, the mol ratio of benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds and adjacent aniline and catalyzer is 1:1:0.01～0.1, the consumption of described solvent is 2mL/mmol benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents,
(2) reaction
The compound of step (1) is carried out chemical reaction, and temperature of reaction is 110～150 ℃, 20～45 hours reaction times;
Its synthetic chemical equation is:
In formula: R
1, R
2Hydrogen, methyl, methoxyl group, chlorine, nitro, fluorine, the tertiary butyl;
X
1Nitrogen hydrogen, oxygen;
X
2N-formyl sarcolysine base, oxygen, sulphur;
(3) separate and extract
Reaction after finishing separates catalyzer; Add entry and ethyl acetate, extracting and demixing in filtrate; Water with the ethyl acetate washing, merges organic phase again;
(4) dry and concentrated
Carry out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product 2-through column chromatography and replace the benzo azole compounds.
Further, the described benzylamine compound of step (1) comprises benzylamine, alpha substituted benzylamine.
Further, the described compound of benzaldehyde category of step (1) comprises phenyl aldehyde, substituted benzaldehyde.
Further, the described phenylcarbinol compounds of step (1) comprises phenylcarbinol, substituted benzyl alcohol.
Further, the described adjacent aniline of step (1) comprises N-methyl-o-phenylenediamine, Ortho-Aminophenol, near amino thiophenols.
Further, described catalyzer is used for the preparation that 2-replaces the benzo azole compounds in the non-oxidation agent or under without the condition of Hydrogen acceptor.
Further, the described solvent of step (1) is the little solvent of water content or anhydrous solvent.
The positively effect that the present invention prepares the method for 2-replacement benzo azole compounds is:
(1) do not need in reaction system to add any oxygenant and Hydrogen acceptor, therefore can not introduce other by products.
(2) the partially catalyzed agent is easy to reclaim, and the catalyzer that reclaims can utilize again, convenient post-treatment.
(3) Atom economy is high, meets the theory of " Green Chemistry ".
Embodiment
Below further introduce the present invention and prepare the embodiment that 2-replaces the method for benzo azole compounds, provide
60Individual embodiment.But enforcement of the present invention is not limited to following embodiment.
Embodiment 1
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixes
Adopting benzylamine and Ortho-Aminophenol is raw material, adopting palladium metal (palladium/carbon 53mg) is catalyzer, with N, the N-N,N-DIMETHYLACETAMIDE is solvent: with benzylamine 107mg(1mmol), Ortho-Aminophenol 109mg(1mmol), palladium/carbon 53mg (0.05mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction
The compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 28h; Its chemical equation is:
(3) separate and extract
Reaction filters out catalyzer after finishing, and adds entry and ethyl acetate, extracting and demixing in filtrate; Water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated
Carrying out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product through column chromatography---2-replaces benzo azole compounds (2-phenyl benzoxazoles) 150mg, and yield is 77%.
The product 2-phenyl benzoxazoles of embodiment 1 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3)：?δ?8.31-8.28?(m,?2?H)，7.82-7.80?(m,?1?H)，7.63-7.61?(m,?1?H)，7.57-7.55?(m,?3?H)，7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3)：δ?109.6，119.0，123.5，?124.1，?126.2，126.6，127.9，130.5，141.1，149.7，162.0；HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684，found?195.0681。
Embodiment 2
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), Ortho-Aminophenol 109mg(1mmol), RuCl
310mg(0.03mmol), DMF 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 38h.
(3) separate and extract: cooling after reaction finishes, add entry and ethyl acetate in reaction solution, extracting and demixing, water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: as to carry out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product through column chromatography---2-replaces benzo azole compounds (2-phenyl benzoxazoles) 156mg, and yield is 80%.
The product 2-phenyl benzoxazoles of embodiment 2 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3)：δ?8.31-8.28?(m,?2?H)，7.82-7.80?(m,?1?H)，7.63-7.61?(m,?1?H)，7.57-7.55?(m，3?H),?7.40-7.38?(m，2?H)；?
13C?NMR?(100MHz,?CDCl
3)：δ?109.6,?119.0，123.5，124.1，?126.2，126.6，?127.9，130.5，141.1，149.7，?162.0；HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment 3～11
Under the experiment condition identical with embodiment 1 and operation, see embodiment 3～11 in lower list 1 with different palladium metal, platinum or ruthenium catalysis benzylamine compound and with the reaction result of Ortho-Aminophenol.
Embodiment 12～16
Under the experiment condition identical with embodiment 2 and operation, see embodiment 12～16 in lower list 1 with different palladium metal or ruthenium catalysis benzylamine compound and with the reaction result of Ortho-Aminophenol.
Table 1. prepares the result of 2-replacement benzo azole compounds take benzylamine compound and Ortho-Aminophenol as raw material:
The product 2-(4-fluorophenyl) benzoxazole of embodiment 4 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.27?(m,?2?H),?7.80-7.78?(m,?1?H),?7.62-7.60?(m,?1?H),?7.40-7.38?(m,?2?H),?7.27-7.22?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?110.6,?116.1,?116.3,?120.0,?124.7,?125.2,?129.8,?129.9,?142.1,?150.8,?162.2,?163.6,?166.1；?HRMS-ESI?Calcd?for?C
13H
8FNO?[M]
+?213.059,?found?213.0588。
The product 2-(4-tert-butyl-phenyl) benzoxazole of embodiment 5 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.21?(d,?2?H，J?=?8.4?Hz),?7.81-7.78?(m,?1?H),?7.62-7.57?(m,?3?H),?7.38-7.36?(m,?2?H),?1.40?(s,?9?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.2,?35.1,?110.5,?119.9,?124.3,?124.5,?124.9,?125.9,?142.2,?150.7,?155.2,?163.3；HRMS-ESI?Calcd?for?C
17H
17NO?[M]
+?251.1310,?found?251.1311。
The product 2-Ben base benzoxazole of embodiment 6 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-Ben base benzoxazole of embodiment 9 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-(4-aminomethyl phenyl) benzoxazole of embodiment 10 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.18?(d,?2?H,?J?=?8.4?Hz),?7.80-7.78?(m,?1?H),?7.61-7.60?(m,?1?H),?7.38-7.35?(m,?4?H),?2.47?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?20.6,?109.5,?118.8,?123.4,?123.5,?123.8.?126.6,?128.6,?141.0,?141.2,?149.7,?162.3；HRMS-ESI?Calcd?for?C
14H
11NO?[M]
+?209.0841,?found?209.0839。
The product 2-(4-aminomethyl phenyl) benzoxazole of embodiment 12 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.18?(d,?2?H,?J?=?8.4?Hz),?7.80-7.78?(m,?1?H),?7.61-7.60?(m,?1?H),?7.38-7.35?(m,?4?H),?2.47?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?20.6,?109.5,?118.8,?123.4,?123.5,?123.8.?126.6,?128.6,?141.0,?141.2,?149.7,?162.3；HRMS-ESI?Calcd?for?C
14H
11NO?[M]
+?209.0841,?found?209.0839。
The product 2-(4-fluorophenyl) benzoxazole of embodiment 13 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.27?(m,?2?H),?7.80-7.78?(m,?1?H),?7.62-7.60?(m,?1?H),?7.40-7.38?(m,?2?H),?7.27-7.22?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?110.6,?116.1,?116.3,?120.0,?124.7,?125.2,?129.8,?129.9,?142.1,?150.8,?162.2,?163.6,?166.1；?HRMS-ESI?Calcd?for?C
13H
8FNO?[M]
+?213.059,?found?213.0588。
The product 2-Ben base benzoxazole of embodiment 14 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment 17
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixes
Adopting benzylamine and N-methyl-o-phenylenediamine is raw material, adopting palladium metal (palladium/carbon 53mg) is catalyzer, take N-methyl second pyrrolidone as solvent: with benzylamine 107mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), palladium/carbon 53mg (0.05mmol), N-methyl second pyrrolidone 2mL add in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction
The compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 20h.
(3) separate and extract
Reaction filters out catalyzer after finishing, and adds entry and ethyl acetate, extracting and demixing in filtrate; Water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated
Carrying out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product through column chromatography---2-replaces benzo azole compounds (1-methyl-2-Phenylbenzimidazole) 177mg, and yield is 85%.
The product 1-methyl-2-Phenylbenzimidazole of embodiment 17 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.87-7.85?(m,?1?H),?7.81-7.79?(m,?2?H),?7.59-7.55?(m,?3?H),?7.44-7.42?(m,?1?H),?7.38-7.32?(m,?2?H),?3.90?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.6,?119.9,?122.5,?122.8,?128.7,?129.5,?129.7,?130.3,?136.6,?143.0,?153.8；?HRMS-ESI?Calcd?for?C
14H
12N
2?[M]
+?208.1,?found?208.0996。
Embodiment 18
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with flunamine 125mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), palladium/carbon 53mg (0.05mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 24h.
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: as to carry out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product through column chromatography---2-replaces benzo azole compounds (1-methyl-2-(4-fluorophenyl) benzoglyoxaline) 208mg, yield is 92%.
The product 1-methyl of embodiment 18 gained-2-(4-fluorophenyl) benzoglyoxaline is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.85-7.83?(m,?1?H),?7.80-7.77?(m,?2?H),?7.44-7.42?(m,?1?H),?7.37-7.35?(m,?2?H),?7.28-7.24?(m,?2?H),?3.89?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.7,?115.8,?116.0,?119.8,?122.6,?122.9,?131.4,?131.5,?136.5,?142.9,?152.8,?162.4,?164.9；?HRMS-ESI?Calcd?for?C
14H
11FN
2?[M]
+?226.0906,?found?226.0903。
Embodiment 19
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), ruthenium/carbon 50mg (0.04mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) (with embodiment 18).
(4) (with embodiment 18) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-Phenylbenzimidazole) 177mg, and yield is 85%.
The product 1-methyl-2-Phenylbenzimidazole of embodiment 19 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.87-7.85?(m,?1?H),?7.81-7.79?(m,?2?H),?7.59-7.55?(m,?3?H),?7.44-7.42?(m,?1?H),?7.38-7.32?(m,?2?H),?3.90?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.6,?119.9,?122.5,?122.8,?128.7,?129.5,?129.7,?130.3,?136.6,?143.0,?153.8；?HRMS-ESI?Calcd?for?C
14H
12N
2?[M]
+?208.1,?found?208.0996。
Embodiment 20
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 2-methylbenzylamine 121mg(1mmol), the adjacent benzene methanamine 122mg(1mmol of N-methyl), ruthenium/carbon 50mg (0.04mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) (with embodiment 18).
(4) (with embodiment 18) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-(2-aminomethyl phenyl) benzoglyoxaline) 197mg, yield is 89%.
Embodiment 21
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), platinum/carbon 80mg (0.02mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 35h.
(3) (with embodiment 18).
(4) (with embodiment 18) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-Phenylbenzimidazole) 184mg, and yield is 88%.
The product 1-methyl-2-Phenylbenzimidazole of embodiment 21 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.87-7.85?(m,?1?H),?7.81-7.79?(m,?2?H),?7.59-7.55?(m,?3?H),?7.44-7.42?(m,?1?H),?7.38-7.32?(m,?2?H),?3.90?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.6,?119.9,?122.5,?122.8,?128.7,?129.5,?129.7,?130.3,?136.6,?143.0,?153.8；?HRMS-ESI?Calcd?for?C
14H
12N
2?[M]
+?208.1,?found?208.0996。
Embodiment 22
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-chlorobenzylamine 141mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), platinum/carbon 80mg (0.02mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 35h.
(3) (with embodiment 18).
(4) (with embodiment 18) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-(4-chloro-phenyl-) benzoglyoxaline) 218mg, yield is 90%.
Embodiment 23
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), Pd (OAc)
22.4mg(0.01mmol), N-Methyl pyrrolidone 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 38h.
(3) after reaction finishes, cooling, add entry and ethyl acetate in reaction solution, extracting and demixing, water with the ethyl acetate washing, merges organic phase again.
(4) (with embodiment 18) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-Phenylbenzimidazole) 156mg, and yield is 75%.
The product 1-methyl-2-Phenylbenzimidazole of embodiment 23 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.87-7.85?(m,?1?H),?7.81-7.79?(m,?2?H),?7.59-7.55?(m,?3?H),?7.44-7.42?(m,?1?H),?7.38-7.32?(m,?2?H),?3.90?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.6,?119.9,?122.5,?122.8,?128.7,?129.5,?129.7,?130.3,?136.6,?143.0,?153.8；?HRMS-ESI?Calcd?for?C
14H
12N
2?[M]
+?208.1,?found?208.0996。
Embodiment 24
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), RuCl
310mg(0.05mmol), DMF 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) (with embodiment 23).
(4) (with embodiment 23) obtains target product---and 2-replaces benzo azole compounds (1-methyl-2-Phenylbenzimidazole) 166mg, and yield is 80%.
The product 1-methyl-2-Phenylbenzimidazole of embodiment 24 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.87-7.85?(m,?1?H),?7.81-7.79?(m,?2?H),?7.59-7.55?(m,?3?H),?7.44-7.42?(m,?1?H),?7.38-7.32?(m,?2?H),?3.90?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.7,?109.6,?119.9,?122.5,?122.8,?128.7,?129.5,?129.7,?130.3,?136.6,?143.0,?153.8；?HRMS-ESI?Calcd?for?C
14H
12N
2?[M]
+?208.1,?found?208.0996。
Embodiment 25
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), near amino thiophenols 125mg(1mmol), palladium/carbon 53mg (0.05mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 28h.
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: as to carry out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product through column chromatography---2-replaces benzo azole compounds (2-phenyl benzothiazole) 149mg, and yield is 85%.
The product 2-phenyl benzothiazole of embodiment 25 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Embodiment 26
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-tert-butyl benzyl amine 163mg(1mmol), near amino thiophenols 125mg(1mmol), palladium/carbon 53mg (0.05mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: (with embodiment 25).
(3) separate and extract: (with embodiment 25).
(4) dry and concentrated: (with embodiment 25) obtains target product---and 2-replaces benzo azole compounds (2-(4-tert-butyl-phenyl) benzothiazole) 254mg, yield is 95%.
The product 2-(4-tert-butyl-phenyl of embodiment 29 gained) benzothiazole is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.10-8.04?(m,?3?H),?7.93?(d,?1?H,?J?=?8?Hz),?7.55-7.49?(m,?3?H),?7.42-7.38?(m,?1?H),?1.40?(s,?9?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.2,?35.0,?121.6,?123.1,?125.0,?126.0,?126.2,?127.4,?130.9,?135.0,?154.2,?154.6,?168.2；?HRMS-ESI?Calcd?for?C
17H
17NS?[M]
+?267.1082,?found?267.1087。
Embodiment 27
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), near amino thiophenols 125mg(1mmol), ruthenium/carbon 50mg (0.04mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) separate and extract: (with embodiment 25).
(4) dry and concentrated: (with embodiment 25) obtains target product---and 2-replaces benzo azole compounds (2-phenyl benzothiazole) 149mg, and yield is 85%.
The product 2-phenyl benzothiazole of embodiment 27 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Embodiment 28
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 3-nitro-benzylamine 152mg(1mmol), near amino thiophenols 125mg(1mmol), ruthenium/carbon 50mg (0.04mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) separate and extract: (with embodiment 25).
(4) dry and concentrated: (with embodiment 25) obtains target product---and 2-replaces benzo azole compounds (2-(3-nitrophenyl) benzothiazole) 218mg, yield is 85%.
Embodiment 29
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), near amino thiophenols 125mg(1mmol), platinum/carbon 80mg (0.02mmol), N, dinethylformamide 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: (with embodiment 28).
(3) separate and extract: (with embodiment 28).
(4) dry and concentrated: (with embodiment 28) obtains target product---and 2-replaces benzo azole compounds (2-phenyl benzothiazole) 149mg, and yield is 85%.
The product 2-phenyl benzothiazole of embodiment 29 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Embodiment 30
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), near amino thiophenols 125mg(1mmol), Pd (OAc)
22.4mg(0.01mmol), DMF 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 38h.
(3) separate and extract: cooling after reaction finishes, add entry and ethyl acetate in reaction solution, extracting and demixing, water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: (with embodiment 28) obtains target product---and 2-replaces benzo azole compounds (2-phenyl benzothiazole) 148mg, and yield is 70%.
The product 2-phenyl benzothiazole of embodiment 30 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Embodiment 31
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with benzylamine 107mg(1mmol), near amino thiophenols 125mg(1mmol), RuCl
310mg(0.05mmol), DMF 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 30h.
(3) separate and extract: (with embodiment 30).
(4) dry and concentrated: (with embodiment 28) obtains target product---and 2-replaces benzo azole compounds (2-phenyl benzothiazole) 160mg, and yield is 76%.
The product 2-phenyl benzothiazole of embodiment 31 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Embodiment 32
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with phenyl aldehyde 106mg(1mmol), Ortho-Aminophenol 109mg(1mmol), palladium/carbon 32mg (0.03mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 110 ℃ of temperature of reaction (oil bath temperature), reaction times 28h, its chemical equation is.
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: use anhydrous sodium sulfate drying, concentrated organic phase obtains target product through column chromatography---and 2-replaces benzo azole compounds (2-phenyl benzoxazoles) 162mg, and yield is 88%.
The product 2-Ben base benzoxazole of embodiment 32 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment 33
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with phenyl aldehyde 106mg(1mmol), Ortho-Aminophenol 109mg(1mmol), Pd (OAc)
24.5mg(0.02mmol), N,N-dimethylacetamide 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 110 ℃ of temperature of reaction (oil bath temperature), reaction times 38h.
(3) separate and extract: reaction adds entry and ethyl acetate after finishing in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: use anhydrous sodium sulfate drying, concentrated organic phase obtains target product through column chromatography---and 2-replaces benzo azole compounds (2-phenyl benzoxazoles) 138mg, and yield is 75%.
The product 2-Ben base benzoxazole of embodiment 33 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment34
～41
Under the experiment condition identical with embodiment 32 and operation, see embodiment 34 in lower list 2 with different palladium metal, platinum or ruthenium catalysis compound of benzaldehyde category and with the reaction result of Ortho-Aminophenol
～41.
Embodiment42
～46
Under the experiment condition identical with embodiment 33 and operation, see embodiment 42 in lower list 2 with different palladium metal or ruthenium catalysis compound of benzaldehyde category and with the reaction result of Ortho-Aminophenol
～46.
Table 2.Prepare the result of 2-replacement benzo azole compounds as raw material take compound of benzaldehyde category and Ortho-Aminophenol
:
。
The product 2-(4-fluorophenyl) benzoxazole of embodiment 34 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.27?(m,?2?H),?7.80-7.78?(m,?1?H),?7.62-7.60?(m,?1?H),?7.40-7.38?(m,?2?H),?7.27-7.22?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?110.6,?116.1,?116.3,?120.0,?124.7,?125.2,?129.8,?129.9,?142.1,?150.8,?162.2,?163.6,?166.1；?HRMS-ESI?Calcd?for?C
13H
8FNO?[M]
+?213.059,?found?213.0588。
The product 2-(4-tert-butyl-phenyl) benzoxazole of embodiment 35 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.21?(d,?2?H，J?=?8.4?Hz),?7.81-7.78?(m,?1?H),?7.62-7.57?(m,?3?H),?7.38-7.36?(m,?2?H),?1.40?(s,?9?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.2,?35.1,?110.5,?119.9,?124.3,?124.5,?124.9,?125.9,?142.2,?150.7,?155.2,?163.3；?HRMS-ESI?Calcd?for?C
17H
17NO?[M]
+?251.1310,?found?251.1311。
The product 2-Ben base benzoxazole of embodiment 36 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-Ben base benzoxazole of embodiment 39 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-(4-aminomethyl phenyl) benzoxazole of embodiment 40 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.18?(d,?2?H,?J?=?8.4?Hz),?7.80-7.78?(m,?1?H),?7.61-7.60?(m,?1?H),?7.38-7.35?(m,?4?H),?2.47?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?20.6,?109.5,?118.8,?123.4,?123.5,?123.8.?126.6,?128.6,?141.0,?141.2,?149.7,?162.3；?HRMS-ESI?Calcd?for?C
14H
11NO?[M]
+?209.0841,?found?209.0839。
Embodiment 42The product 2-(4-aminomethyl phenyl) benzoxazole of gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.18?(d,?2?H,?J?=?8.4?Hz),?7.80-7.78?(m,?1?H),?7.61-7.60?(m,?1?H),?7.38-7.35?(m,?4?H),?2.47?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?20.6,?109.5,?118.8,?123.4,?123.5,?123.8.?126.6,?128.6,?141.0,?141.2,?149.7,?162.3；?HRMS-ESI?Calcd?for?C
14H
11NO?[M]
+?209.0841,?found?209.0839。
The product 2-Ben base benzoxazole of embodiment 44 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment 47
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-chlorobenzaldehyde 140mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), ruthenium/carbon 30mg, N-Methyl pyrrolidone 2mL add in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 120 ℃ of temperature of reaction (oil bath temperature), reaction times 25h.
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: use anhydrous sodium sulfate drying, concentrated organic phase obtains target product through column chromatography---and 2-replaces benzo azole compounds (1-methyl-2-(4-chloro-phenyl-) benzoglyoxaline) 206mg, yield is 85%.
Embodiment 48
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-methoxybenzaldehyde 136mg(1mmol), near amino thiophenols 125mg(1mmol), Pd (OAc)
24.5mg(0.02mmol), N-Methyl pyrrolidone 2mL adds in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 110 ℃ of temperature of reaction (oil bath temperature), reaction times 35h.
(3) separate and extract: (with embodiment 47).
(4) dry and concentrated: (with embodiment 47) obtains target product---and 2-replaces benzo azole compounds (2-(4-p-methoxy-phenyl) benzothiazole) 205mg, yield is 85%.
The product 2-(4-p-methoxy-phenyl of embodiment 48 gained) benzothiazole is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.07-8.05?(m,?3?H),?7.91?(d,?1?H,?J?=?7.6?Hz),?7.52-7.48?(m,?1?H),?7.40-7.36?(m,?1?H),?7.03?(d,?2?H,?J=8.8?Hz),?3.91?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?54.4,?113.3,?120.5,?121.8,?123.8,?125.2,?125.4,?128.1,?133.8,?153.2,?160.9,?166.8；?HRMS-ESI?Calcd?for?C
14H
11NOS?[M]
+?241.0561,?found?241.0556。
Embodiment 49
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixes: with phenylcarbinol 108mg(1mmol), Ortho-Aminophenol 109mg (1mmol), palladium/carbon 53mg, N,N-dimethylacetamide 2mL add in there-necked flask successively, stirs under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 130 ℃ of temperature of reaction (oil bath temperature), reaction times 35h; Its chemical equation is:
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: use anhydrous sodium sulfate drying, concentrated organic phase obtains target product through column chromatography---and 2-replaces benzo azole compounds (2-phenyl benzoxazoles) 162mg, and yield is 83%.
The product 2-Ben base benzoxazole of embodiment 49 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
Embodiment 50～57
Under the experiment condition identical with embodiment 49 and operation, see embodiment 50～57 in lower list 3 with different palladium metal, platinum or ruthenium catalytic phenylmethanol compounds and with the reaction result of Ortho-Aminophenol.
Table 3. prepares the result of 2-replacement benzo azole compounds take phenylcarbinol compounds and Ortho-Aminophenol as raw material:
The product 2-(4-fluorophenyl) benzoxazole of embodiment 50 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.27?(m,?2?H),?7.80-7.78?(m,?1?H),?7.62-7.60?(m,?1?H),?7.40-7.38?(m,?2?H),?7.27-7.22?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?110.6,?116.1,?116.3,?120.0,?124.7,?125.2,?129.8,?129.9,?142.1,?150.8,?162.2,?163.6,?166.1；?HRMS-ESI?Calcd?for?C
13H
8FNO?[M]
+?213.059,?found?213.0588。
The product 2-Ben base benzoxazole of embodiment 52 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-Ben base benzoxazole of embodiment 55 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.31-8.28?(m,?2?H),?7.82-7.80?(m,?1?H),?7.63-7.61?(m,?1?H),?7.57-7.55?(m,?3?H),?7.40-7.38?(m,?2?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?109.6,?119.0,?123.5,?124.1,?126.2,?126.6,?127.9,?130.5,?141.1,?149.7,?162.0；?HRMS-ESI?Calcd?for?C
13H
9NO?[M]
+?195.0684,?found?195.0681。
The product 2-(4-aminomethyl phenyl) benzoxazole of embodiment 56 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.18?(d,?2?H,?J?=?8.4?Hz),?7.80-7.78?(m,?1?H),?7.61-7.60?(m,?1?H),?7.38-7.35?(m,?4?H),?2.47?(s,?3?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?20.6,?109.5,?118.8,?123.4,?123.5,?123.8.?126.6,?128.6,?141.0,?141.2,?149.7,?162.3；?HRMS-ESI?Calcd?for?C
14H
11NO?[M]
+?209.0841,?found?209.0839。
Embodiment 58
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-nitrobenzyl alcohol 153mg(1mmol), near amino thiophenols 125mg(1mmol), palladium/carbon 106mg (0.1mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 140 ℃ of temperature of reaction (oil bath temperature), reaction times 40h.
(3) separate and extract: reaction filters out catalyzer after finishing, and adds entry and ethyl acetate in filtrate, extracting and demixing, and water with the ethyl acetate washing, merges organic phase again.
(4) dry and concentrated: use anhydrous sodium sulfate drying, concentrated organic phase obtains target product through column chromatography---and 2-replaces benzo azole compounds (2-(4-nitrophenyl) benzothiazole) 223mg, yield is 87%.
Embodiment 59
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with 4-tert.-butylbenzene methyl alcohol 164mg(1mmol), N-methyl-o-phenylenediamine 122mg(1mmol), ruthenium/carbon 90mg (0.08mmol), N, N-N,N-DIMETHYLACETAMIDE 2mL adds in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 150 ℃ of temperature of reaction (oil bath temperature), reaction times 45h.
(3) separate and extract: (with embodiment 58).
(4) dry and concentrated: (with embodiment 58) obtains target product---and 2-replaces benzo azole compounds (2-(4-tert-butyl-phenyl) benzoglyoxaline) 224mg, yield is 85%.
The product 2-(4-tert-butyl-phenyl of embodiment 59 gained) benzoglyoxaline is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?7.86-7.83?(m,?1?H),?7.74?(d,?2?H,?J?=?8.8?Hz),?7.58-7.56?(m,?2?H),?7.43-7.41?(m,?1?H),?7.36-7.33?(m,?2?H),?3.91?(s,?3?H),?1.41?(s,?9?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?31.3,?31.7,?34.9,?109.5,?119.8,?122.3,?122.6,?125.6,?127.2,?129.2,?136.6,?143.0,?153.0,?153.9；?HRMS-ESI?Calcd?for?C
18H
20N
2?[M]
+?264.1626,?found?264.1627。
Embodiment 60
A kind of method for preparing 2-replacement benzo azole compounds comprises the following steps:
(1) raw material mixing: with phenylcarbinol 108mg(1mmol), near amino thiophenols 125mg(1mmol), platinum/carbon 240mg (0.09mmol), N-Methyl pyrrolidone 2mL add in there-necked flask successively, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents.
(2) reaction: the compound of step (1) is carried out chemical reaction, 130 ℃ of temperature of reaction (oil bath temperature), reaction times 42h.
(3) separate and extract: (with embodiment 58).
(4) dry and concentrated: (with embodiment 58) obtains target product---and 2-replaces benzo azole compounds (2-phenyl benzothiazole) 179mg, and yield is 85%.
The product 2-phenyl benzothiazole of embodiment 60 gained is through the Structural Identification of nuclear-magnetism, high resolution mass spectrum, and its result is:
1H?NMR?(400MHz,?CDCl
3):?δ?8.13-8.10?(m,?3?H),?7.94?(d,?1?H,?J?=?8.0?Hz),?7.54-7.51?(m,?4?H),?7.44-7.40?(m,?1?H)；?
13C?NMR?(100MHz,?CDCl
3):?δ?121.6,?123.2,?125.2,?126.3,?127.6,?129.0,?131.0,?133.6,?135.1,?154.2,?168.1；?HRMS-ESI?Calcd?for?C
13H
9NS?[M]
+?211.0456,?found?211.0454。
Claims (1)
1. prepare the method that 2-replaces the benzo azole compounds, it is characterized in that, comprise the following steps:
(1) raw material mixes
adopt benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds, and adjacent aniline is raw material, adopt palladium metal, platinum or ruthenium are catalyzer, with N, dinethylformamide, N, N-N,N-DIMETHYLACETAMIDE or N-Methyl pyrrolidone are solvent, add benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds successively in there-necked flask, and adjacent aniline, catalysts and solvents, the mol ratio of benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds and adjacent aniline and catalyzer is 1:1:0.01～0.1, the consumption of described solvent is 2mL/mmol benzylamine compound or compound of benzaldehyde category or phenylcarbinol compounds, stir under nitrogen atmosphere, raw material is mixed with catalysts and solvents,
(2) reaction
The compound of step (1) is carried out chemical reaction, and temperature of reaction is 110～150 ℃, 20～45 hours reaction times;
Its synthetic chemical equation is:
In formula: R
1, R
2Hydrogen, methyl, methoxyl group, chlorine, nitro, fluorine, the tertiary butyl;
X
1Nitrogen hydrogen, oxygen;
X
2N-formyl sarcolysine base, oxygen, sulphur;
(3) separate and extract
Reaction after finishing separates catalyzer; Add entry and ethyl acetate, extracting and demixing in filtrate; Water with the ethyl acetate washing, merges organic phase again;
(4) dry and concentrated
Carry out drying and concentrated with the organic phase that anhydrous sodium sulphate obtains step (3), obtain target product 2-through column chromatography and replace the benzo azole compounds.
2. the method for preparing 2-replacement benzo azole compounds according to claim 1, is characterized in that, the described benzylamine compound of step (1) comprises benzylamine, alpha substituted benzylamine.
3. the method for preparing 2-replacement benzo azole compounds according to claim 1, is characterized in that, the described compound of benzaldehyde category of step (1) comprises phenyl aldehyde, substituted benzaldehyde.
4. the method for preparing 2-replacement benzo azole compounds according to claim 1, is characterized in that, the described phenylcarbinol compounds of step (1) comprises phenylcarbinol, substituted benzyl alcohol.
5. the method for preparing 2-replacement benzo azole compounds according to claim 1, is characterized in that, the described adjacent aniline of step (1) comprises N-methyl-o-phenylenediamine, Ortho-Aminophenol, near amino thiophenols.
6. according to claim 1ly prepare the method that 2-replaces the benzo azole compounds, it is characterized in that, described catalyzer is used for the preparation that 2-replaces the benzo azole compounds under in the non-oxidation agent or without the condition of Hydrogen acceptor.
7. the method for preparing 2-replacement benzo azole compounds according to claim 1, is characterized in that, described solvent is the little solvent of water content or anhydrous solvent.
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