Method for amide alcoholysis

Abstract

The invention provides a method for amide alcoholysis. The method comprises the following steps: using an epoxy compound as an accelerator, and performing alcoholysis on an amide-containing compound under an alkaline condition. The above method is convenient and easy to operate, pure products can be obtained through post-treatment which just needs conventional separation steps, and the epoxy compound is low in costs, thus production and operation costs and three wastes (waste water, waste gas and solid waste) treatment risks and costs can be greatly reduced; when the above method is used, reaction conditions are mild, the method can be compatible with various substituent groups and functional groups, obtains good yields aiming at various amides with different structures, and is wide in substrate application range; an environmentally friendly, economic and practical high-efficiency method for conversion of amides into more useful esters is provided; and the above alcoholysis reaction cannot be influenced by impurities of a previous-step C-H activating reaction system, an intermediate purification step is saved, and two-step reactions of a C-H activating reaction and an amide alcoholysis reaction can be linked.

Description

technical field

[0001] The invention relates to the field of organic material synthesis, in particular to a method for alcoholysis of amides. Background technique

[0002] As a common functional group, the amide bond widely exists in natural products such as proteins and synthetic compounds. It is generally believed that the resonance stability of the amide bond makes the amide a weaker electrophile (The structure of proteins: two hydrogen bonded helical configurations of the polypeptidechain. Proc. Natl. Acad. Sci. 1951, 37, 205), so that it is difficult to use The chemical synthesis method selectively opens the C-N bond of amides (Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds. Nature 2015, 524, 79).

[0003] -CONHAr F (Ar F =p-CF 3 C 6 f 4 ) as an excellent amide directing group has a very wide range of applications in various types of β-C–H activation reactions, but its disadvantage is that for some substrates, the directing gr...

Examples

Embodiment 1

[0049] Add a1 (87.5 mg, 0.2 mmol), potassium acetate (19.6 mg, 0.2 mmol), absolute ethanol (2.0 mL, containing <0.01 wt%), methyl Glycidyl ether b1 (52.9mg, 0.6mmol), forming a reaction system. The above-mentioned Schlenck tube was placed in an oil bath at 90° C. for a heating reaction for 35 hours. TLC showed that the reaction of the raw materials was complete, and the product system was obtained. The product system was stopped from heating and cooled to room temperature, and the solvent was removed under reduced pressure to obtain a residue. 2.0 mL of purified water was added to the residue to form a mixture, and the pH of the mixture was adjusted to 4 with 3M hydrochloric acid while stirring, and then washed with n-hexane (3 mL× 3) The organic phase was obtained by extraction, and the combined organic phase was dried with anhydrous sodium sulfate, filtered after drying, and the filtrate was concentrated to obtain 45.5 mg of pure product, with a yield of 92%.

[0050] The c...

Embodiment 2

[0055] The difference from Example 1 is that, after increasing the amount of each material in Example 1 by 100 times, a 500mL pressure reactor was used to carry out the alcoholysis reaction, and the filtrate was concentrated to obtain 4.648g of pure product with a yield of 94%. Example 2 The yield is greater than that of Example 1, because the adhesion loss is large during a small amount of reaction operation in Example 1, and the yield is more accurate during a large amount of reaction.

Embodiment 3

[0057] The difference from Example 1 is that the molar ratio of methyl glycidyl ether b1 and a1 is 5:1, and the yield is 93%.

technical field

[0001] The invention relates to the field of organic material synthesis, in particular to a method for alcoholysis of amides. Background technique

[0002] As a common functional group, the amide bond widely exists in natural products such as proteins and synthetic compounds. It is generally believed that the resonance stability of the amide bond makes the amide a weaker electrophile (The structure of proteins: two hydrogen bonded helical configurations of the polypeptidechain. Proc. Natl. Acad. Sci. 1951, 37, 205), so that it is difficult to use The chemical synthesis method selectively opens the C-N bond of amides (Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds. Nature 2015, 524, 79).

[0003] -CONHAr F (Ar F =p-CF 3 C 6 f 4 ) as an excellent amide directing group has a very wide range of applications in various types of β-C–H activation reactions, but its disadvantage is that for some substrates, the directing gr...

Examples

Embodiment 1

[0049] Add a1 (87.5 mg, 0.2 mmol), potassium acetate (19.6 mg, 0.2 mmol), absolute ethanol (2.0 mL, containing <0.01 wt%), methyl Glycidyl ether b1 (52.9mg, 0.6mmol), forming a reaction system. The above-mentioned Schlenck tube was placed in an oil bath at 90° C. for a heating reaction for 35 hours. TLC showed that the reaction of the raw materials was complete, and the product system was obtained. The product system was stopped from heating and cooled to room temperature, and the solvent was removed under reduced pressure to obtain a residue. 2.0 mL of purified water was added to the residue to form a mixture, and the pH of the mixture was adjusted to 4 with 3M hydrochloric acid while stirring, and then washed with n-hexane (3 mL× 3) The organic phase was obtained by extraction, and the combined organic phase was dried with anhydrous sodium sulfate, filtered after drying, and the filtrate was concentrated to obtain 45.5 mg of pure product, with a yield of 92%.

[0050] The c...

Embodiment 2

[0055] The difference from Example 1 is that, after increasing the amount of each material in Example 1 by 100 times, a 500mL pressure reactor was used to carry out the alcoholysis reaction, and the filtrate was concentrated to obtain 4.648g of pure product with a yield of 94%. Example 2 The yield is greater than that of Example 1, because the adhesion loss is large during a small amount of reaction operation in Example 1, and the yield is more accurate during a large amount of reaction.

Embodiment 3

[0057] The difference from Example 1 is that the molar ratio of methyl glycidyl ether b1 and a1 is 5:1, and the yield is 93%.

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