Alkylation method for nitrogen-hydrogen containing compounds and application thereof

A technology of compound and alkylation, which is applied in the preparation of organic compounds, preparation of amino compounds, chemical instruments and methods, etc., can solve problems that have not been reported in the research, and achieve high reaction efficiency, mild reaction conditions and high tolerance Effect

Active Publication Date: 2018-09-07
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, the research on N,N-dimethylformamide dialkyl acetals has mainly focused on the condensation reaction and carboxylation reaction on active hydrogen, while the nitrogen alkylation of N-H heterocyclic compounds Reaction studies have not been reported

Method used

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  • Alkylation method for nitrogen-hydrogen containing compounds and application thereof
  • Alkylation method for nitrogen-hydrogen containing compounds and application thereof
  • Alkylation method for nitrogen-hydrogen containing compounds and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Preparation of 1-methyl-3,4-dihydroquinazolin-2(1H)-one

[0031]

[0032] To 3,4-dihydroquinazolin-2(1H)-one (1.7g, 11.6mmol) in DMF solution (10ml) was added dropwise N,N-dimethylformamide dimethyl acetal (5.5 g, 46.3mmol), react at 80°C for 2h. Water (28ml) and ethyl acetate (15ml) were added to separate the layers, the aqueous layer was extracted with ethyl acetate (15×2ml), the organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was decompressed Concentrate to obtain a crude product, which is separated by column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain 1.6 g of white solid, which is relative to 3,4-dihydroquinazoline-2(1H)- The yield of ketone is 91.8%. The purity of the product is 99.6% (mass fraction), MS (ESI) (m / z): 161.2 (M+H) + . 1 H-NMR(CDCl 3 , 400MHz) δ: 7.15 (m, 1H), 7.08-7.11 (m, 2H), 6.93 (m, 1H), 3.42 (s, 3H), 2.86 (t, 2H), 2.49 (t, 2H).

Embodiment 2

[0033] Example 2 Preparation of 1-ethyl-3,4-dihydroquinazolin-2(1H)-one

[0034]

[0035] To 3,4-dihydroquinazolin-2(1H)-one (0.3g, 2.0mmol) in DMF solution (4ml) was added dropwise N,N-dimethylformamide diethyl acetal (1.0 g, 8.2mmol), react at 80°C for 2h. Add water (10ml) and ethyl acetate (10ml), separate the layers, extract the aqueous layer with ethyl acetate (10×2ml), combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, filter, and reduce the filtrate Concentrate to obtain a crude product, which is separated by column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain a white solid (0.32 g, yield 89.8%). The purity of the product is 99.4% (mass fraction), MS (ESI) (m / z): 175.1 (M+H) + . 1 H-NMR(CDCl 3 , 400MHz) δ: 7.15 (m, 1H), 7.08-7.11 (m, 2H), 6.93 (m, 1H), 4.42 (m, 2H), 2.86 (t, 2H), 2.49 (t, 2H), 1.49 (t,3H).

Embodiment 3

[0036] Example 3 Preparation of 1-isopropyl-3,4-dihydroquinazolin-2(1H)-one

[0037]

[0038] To 3,4-dihydroquinazolin-2(1H)-one (0.7g, 4.7mmol) in DMF solution (4ml) was added dropwise N,N-dimethylformamide diisopropyl acetal ( 3.2g, 27.2mmol), reacted at 80°C for 2h. Add water (18ml) and ethyl acetate (15ml), separate the layers, extract the aqueous layer with ethyl acetate (15×2ml), combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, filter, and reduce the filtrate Concentrate to obtain a crude product, which is separated by column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain a white solid (0.75 g, yield 84.2%). The purity of the product is 99.5% (mass fraction), MS (ESI) (m / z): 189.1 (M+H) + . 1 H-NMR(CDCl 3 , 400MHz) δ: 7.15 (m, 1H), 7.08-7.11 (m, 2H), 6.93 (m, 1H), 3.80 (m, 1H), 2.86 (t, 2H), 2.49 (t, 2H), 1.32 (d, 6H).

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Abstract

The invention discloses an alkylation method for nitrogen-hydrogen containing compounds and an application thereof, belonging to the technical field of synthesis of organic compounds. The invention provides a series of methods for a nitrogen alkylation reaction of N-H containing heterocyclic compounds (II) with N,N-dimethylformamide dialkyl acetal as an alkyl source under the condition of no participation of metals, and a product with a hydrogen atom on a nitrogen atom substituted by R1 is obtained. The method provided by the invention has the advantages of highly-efficient reaction, high yield, simple treatment after the reaction, simple and convenient operation, mild reaction conditions, no participation of the metals, high tolerance of functional groups of a reaction substrate, wide range and easy preparation of the substrate, high reaction efficiency after amplification of the reaction, and applicability to large-scale industrial production.

Description

Technical field [0001] The invention relates to an alkylation method and application of nitrogen-containing hydrogen compounds, and belongs to the technical field of organic compound synthesis. Background technique [0002] N-H-containing heterocyclic compounds are a very important organic synthesis intermediate, and the nitrogen atom alkylation reaction in N-H-containing heterocyclic compounds is an important way to synthesize such compounds. The most commonly used alkylating reagents for the alkylation of nitrogen atoms in N-H heterocyclic compounds include halogenated hydrocarbons, sulfate esters, and sulfonate esters. The method of using halogenated hydrocarbons as alkylating reagents is that substrates and strong bases (sodium carbonate, n-butyllithium, sodium tert-butoxide, etc.) formed at low temperature will nucleophilic attack on halogenated hydrocarbons. Alkane substituted products. However, this method has harsh reaction conditions, is cumbersome to operate, and prod...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/227C07D249/18C07D233/58C07D233/91C07C209/00C07C211/48C07D207/323C07D231/12C07D209/08C07D231/56C07D235/06C07D209/34C07D217/04C07D215/48C07C221/00C07C223/02
CPCC07C209/00C07C221/00C07D207/323C07D209/08C07D209/34C07D215/227C07D215/48C07D217/04C07D231/12C07D231/56C07D233/58C07D233/91C07D235/06C07D249/18C07C223/02C07C211/48
Inventor 唐春雷赵辉胡小霞冯柏年张艳张月刘延革胡旭阳李沛伶
Owner JIANGNAN UNIV
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