Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof

A technology of hydroxymethylquinoline and methylquinoline, which is applied in the field of preparation of 2-methyl-4-hydroxymethylquinoline derivatives, can solve the problems of low universality and poor functional group tolerance, etc. Achieve the effects of strong controllability, less side reaction products and high reaction yield

Active Publication Date: 2019-05-21
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The generalizability of the reaction is not high due to the poor tolerance of functional groups in the substrate due to the strong oxidizing properties of peroxides

Method used

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  • Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof
  • Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof
  • Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] 2-Methylquinoline (1 mmol, 143 mg), Selectfluor (2 mmol, 0.7 g) and AgNO 3 (1mmol, 167mg) was added to an aqueous solution of methanol (10ml, MeOH:H 2 O=4:1) and reacted at 80°C for 3h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3*20 mL), combined organic layers, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate , filtered and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 3:2) yielded 140 mg of the product 2-methyl-4-hydroxymethylquinoline with a yield of 81%.

[0031] 1 H NMR (600MHz, CDCl 3 ) δ ppm 8.02 (d, J = 8.4 Hz, 1H), 7.86 (d, J =8.2 Hz, 1H), 7.68 – 7.62 (m, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.41 ( s, 1H), 5.18 (s, 2H), 2.64 (s, 3H).; 13 C NMR (151 MHz, CDCl 3 ) δ ppm 158.95, 147.12, 146.77, 129.38, 128.68, 125.85, 124.06, 122.66, 119.07, 61.17, 25.10.; HRMS(ESI) Calcd. for C 11 h 12 NO [(M+H) + ] 174.0913, found 174.0912.

Embodiment 2

[0033] 2-Methyl-6-fluoroquinoline (1 mmol, 161 mg), Selectfluor (2 mmol, 0.7 g) and AgNO 3 (1mmol, 167mg) was added to an aqueous solution of methanol (10ml, MeOH:H 2 O=4:1) and reacted at 80°C for 3h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3*20 mL), combined organic layers, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate , filtered and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 3:2) yielded 172 mg of the product 2-methyl-4-hydroxymethyl-6-fluoroquinoline with a yield of 90%.

[0034] 1 H NMR (600MHz, CDCl 3 ) δ ppm 8.03 (dd, J = 9.2, 5.5 Hz, 1H), 7.51 (dd, J = 9.8, 2.8 Hz, 1H), 7.46 – 7.41 (m, 2H), 5.12 (s, 2H), 2.71 (s , 3H).; 13 CNMR (151 MHz, CDCl 3 ) Δ PPM 160.81, 159.18, 158.32, 158.30, 145.52, 144.63,131.44, 131.38, 124.80, 124.73, 119.86, 119.18, 106.54,61.57, 25.19.; 11 h 11 FNO [(M+H) + ] 192.0819, found 192.0819.

Embodiment 3

[0036] 2-Methyl-6-chloroquinoline (1 mmol, 177 mg), Selectfluor (2 mmol, 0.7 g) and AgNO 3 (1mmol, 167mg) was added to an aqueous solution of ethanol (10ml, EtOH:H 2 O=4:1) and reacted at 80°C for 3h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3*20 mL), combined organic layers, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate , filtered and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 1:1) yielded 108 mg of the product 2-methyl-4-(1-ethanol-yl)-6-chloroquinoline with a yield of 49%.

[0037] 1 H NMR (600MHz, CDCl 3 ) δ ppm 7.86 (dd, J = 5.6, 3.1 Hz, 2H), 7.53 (dd, J = 9.0, 2.2 Hz, 1H), 7.41 (s, 1H), 5.45 (q, J = 6.5 Hz, 1H), 4.23 – 4.17 (m,1H), 2.60 (s, 3H), 1.59 (d, J = 6.6 Hz, 3H).; 13 C NMR (151 MHz, CDCl 3 for C 12 h 13 ClNO [(M+H) + ] 222.0680, found 222.0682.

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Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for reacting 2-methylquinoline and derivatives thereof with primary alcohol. The method is carried out by the following steps of: under the catalysis of Selectfluor/AgNO3, reacting the 2-methylquinoline and the derivatives in a primary alcohol aqueous solution, and performing column chromatography to obtain a product of dehydrogenation coupling of 4-position and alcohol compounds of the 2-methylquinoline derivatives. The method provided by the invention is carried out in a mixed solution ofwater and alcohol compounds under the catalysis of Selectfluor/AgNO3, and has the advantages of good substrate solubility, wide applicability, high reaction yield and strong controllability. The method is green and environment-friendly, and has the advantages of few side reaction products, green and high efficiency.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a preparation method of 2-methyl-4-hydroxymethylquinoline derivatives. Background technique [0002] Quinoline compounds with hydroxymethyl groups have good biological activity, so the efficient synthesis of such compounds has important application value. Common synthetic methods all use strong oxidants (such as ammonium peroxide, sodium peroxide, benzoyl peroxide and catalysts in combination, etc.). [0003] [0004] The generalizability of the reaction is not high due to the poor tolerance of functional groups in the substrate due to the strong oxidative properties of peroxides. Therefore, it is an urgent problem to develop a preparation method with simple synthesis method and low substrate requirement. Contents of the invention [0005] Aiming at the problems existing in the prior art, the invention discloses a preparation method of 2-methyl-4-hyd...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/14C07D215/18
Inventor 王守锋范亚飞王文贵
Owner UNIV OF JINAN
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