Preparation method of N-alkynyl benzimidazole derivatives

A technology of alkynyl benzimidazole and benzimidazole is applied in the field of preparation of N-alkynyl benzimidazole derivatives, and can solve the problems of complicated steps, high environmental pollution of metal salts, and difficulty in obtaining raw materials.

Active Publication Date: 2015-11-25
HUNAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the shortcomings of these methods are also obvious, mainly reflected in: (1) raw materials are difficult to obtain; (2) metal salts are more polluting to the environment; (3) the steps are cumbersome

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  • Preparation method of N-alkynyl benzimidazole derivatives
  • Preparation method of N-alkynyl benzimidazole derivatives

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preparation example Construction

[0024] A preparation method of N-alkynylbenzimidazole derivatives, comprising the following steps:

[0025] Under the atmosphere of protective gas, lithium hexamethyldisilazide, diethyl chlorophosphate and lithium hexamethyldisilazide were sequentially added to 1-R shown in general formula 2 1 Formylmethyl 2-R 2 Reaction in the anhydrous solvent of basebenzimidazole, obtains the N-alkynylbenzimidazole derivative shown in general formula 1;

[0026]

[0027] Among them, when adding LiHMDS to react, the temperature is controlled at -78~0°C; adding ClP(O)(OEt) 2 Afterwards, the system is heated to 10-30°C for reaction, R 1 For phenyl, 4-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 2,5-dimethoxyphenyl, 3,4-methylenedioxybenzene, 4- One of fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-naphthyl, 6-methoxy-2-naphthyl, thienyl, tert-butyl, R 2 For furyl, H, propyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 3,4-methylenedioxybenzene, 4-chlorophenyl, 4-nitropheny...

Embodiment 1

[0044] R 1 =Ph, R 2 =2-furyl

[0045] Dissolve 2-furylbenzimidazole (184.06mg, 1.0mmol) and α-bromoacetophenone (237.6mg, 1.2mmol) in anhydrous acetone (20mL), and add anhydrous potassium carbonate (165.6mg, 1.2mmol), reflux, TLC tracking reaction (about 12h), after all the raw materials have reacted, the mixture was poured into a large amount of water to wash, extracted with dichloromethane (30mL×3), the organic phase was washed with saturated brine, anhydrous sulfuric acid After drying over sodium, after filtration, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 5:1] to obtain 265.9 mg of substrate 2a, with a yield of 88.2%.

[0046] 2a White solid, 150~151℃

[0047] 1 HNMR (400MHz, DMSO) δ8.17 (d, J = 7.4Hz, 2H), 7.81–7.74 (m, 2H), 7.67 (dt, J = 14.6, 7.2Hz, 4H), 7.27 (d, J = 3.7 Hz,2H),7.18(d,1H),6.67(m,1H),6.27(s,2H).

[0048] MS(EI)m / z(%):302(M + ,100). ...

Embodiment 2

[0050] Preparation 1a

[0051] The chemical structure of 1a is as follows

[0052]

[0053] Under the protection of nitrogen at 0°C, LiHMDS (0.75 mL of 1.0 mol / L solution in THF) was added dropwise to a solution of substrate 2a (151.5 mg, 0.5 mmol) in THF (10 mL), and stirred for 15 minutes. ClP(O)(OEt) 2 (0.13mL, 1.0mmol) was added dropwise into the above reaction system. After the dropwise addition was complete, the cooling device was removed, the temperature was raised to 10° C. and stirring was continued for 2 hours. The reaction was cooled to 0°C again, and then LiHMDS (1.0 mL of tetrahydrofuran solution with a concentration of 1.0 mol / L) was added dropwise to the above reaction system, and stirring was continued at this temperature for 2 hours. The reaction was quenched with saturated ammonium chloride solution, the reaction mixture was poured into water, extracted with ethyl acetate (30mL×3), the organic phase was washed with saturated brine, dried over anhydrous ...

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Abstract

The invention discloses a preparation method of N-alkynyl benzimidazole derivatives, which comprises the following step: under the atmosphere of protective gas, sequentially adding LiHMDS, diethyl chlorophosphate and LiHMDS into an anhydrous solvent of 1-R1 formyl-methyl 2-R2 benzimidazole as shown in the general formula 2 so as to react to obtain an N-alkynyl benzimidazole derivative as shown in the general formula 1, wherein when LiHMDS is added for reacting, the temperature is controlled at -78-0 DEG C, and after ClP(O)(OEt)2 is added, the system temperature rises to 10-30 DEG C so as to react. The preparation method of the N-alkynyl benzimidazole derivatives has the advantages that (1) substrates can be conveniently prepared through cheap raw materials; (2) the universality is good, and preparation of benzimidazole alkyne amine derivatives containing different substituent combinations can be easily realized; (3) the operation is simple and convenient, and the separation of intermediates is not needed; and (4) target compounds are easy to separate and purify, and the yield is relatively high.

Description

technical field [0001] The invention relates to benzimidazole alkyne amine derivatives, in particular to a preparation method of N-alkynyl benzimidazole derivatives. Background technique [0002] Benzimidazole alkyne amine derivatives contain the basic structures of alkynes and benzimidazoles, and have the basic properties of these two types of compounds. They are very important intermediates in organic synthesis. It plays an important role in organic synthesis and biochemistry, and these compounds have biological characteristics and photoconductive properties. [0003] The synthetic method bibliographical report of relevant benzimidazole alkyne amine derivative is mainly elimination method (Katritzky, A.R. etc. J.Org.Chem.2002,67,7526-7529), alkynyl isomerization (Huang, J. etc. Org. Lett. 2002, 4, 2417.), alkyniodonium salt coupling (Kitamura, T. et al. Heterocycles 2000, 52, 303), metal catalysis (Burley, G.A.; et al. J. Org. Chem. 2010, 75, 980.). But the shortcomings ...

Claims

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Application Information

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IPC IPC(8): C07D405/04C07D405/14C07D409/14C07D235/06C07D235/08C07D235/18
CPCC07D235/06C07D235/08C07D235/18C07D405/04C07D405/14C07D409/14
Inventor 安德烈张艳勤董万荣
Owner HUNAN UNIV
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