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CN-122010761-A - Alkene-containing amide skeleton (E) -alkoxycarbonyl derivative and preparation method thereof

CN122010761ACN 122010761 ACN122010761 ACN 122010761ACN-122010761-A

Abstract

The invention discloses an enamide skeleton-containing (E) -alkoxycarbonyl derivative and a preparation method thereof, wherein the molecular structure of the derivative is as follows: Wherein R 1 is phenyl, alkyl, alkoxy, halogen or thiomethyl, R 2 is benzyl, methyl, acyl or tert-butoxycarbonyl, and R 3 is alkyl. The preparation method comprises the steps of mixing a non-cyclic alkylamide compound, hydrazino formate, an additive, an electrolyte and a solvent in a reactor equipped with an electrode slice, and carrying out beta-C (sp 2 ) -H alkoxycarbonyl reaction under electrochemical conditions to obtain a series E-type beta-alkoxycarbonyl enamide derivative with high selectivity. The method adopts the current as the oxidant, does not need to add various metal catalysts and chemical oxidants, has mild reaction conditions, good stereoselectivity of the obtained product, simple and feasible whole process, simple reaction system and small pollution, accords with the green chemical concept and has good application potential.

Inventors

  • LUO HAIQING
  • CHEN GUISHENG
  • FAN LILI

Assignees

  • 赣南师范大学

Dates

Publication Date
20260512
Application Date
20260203

Claims (9)

  1. 1. The (E) -alkoxycarbonyl derivative containing the enamide skeleton is characterized by comprising the following molecular structures: ; Wherein R 1 is phenyl, alkyl, alkoxy, halogen or thiomethyl, R 2 is benzyl, methyl, acyl or tert-butoxycarbonyl, and R 3 is alkyl.
  2. 2. The enamide skeleton (E) -alkoxycarbonyl derivative according to claim 1, wherein the enamide skeleton (E) -alkoxycarbonyl derivative comprises: 。
  3. 3. A process for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 1 or 2, wherein the process comprises mixing a non-cyclic alkylamide compound, a hydrazinoformate, an additive, an electrolyte and a solvent in a reactor equipped with an electrode sheet, and performing beta-C (sp 2 ) -H alkoxycarbonyl reaction under electrochemical conditions to obtain a series of E-type beta-alkoxycarbonylamide derivatives with high selectivity; the non-cyclic alkylamide compound has the following formula The structure is shown; The hydrazinoformate has The structure is shown; The additive is selected from any one or more than two of nitric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, potassium carbonate, potassium bicarbonate and sodium acetate; The electrolyte is selected from any one or a mixture of more than two of n Bu 4 NBF 4 , n Bu 4 NClO 4 , n Bu 4 NI, n Bu 4 NH 2 PO 4 , n Bu 4 NPF 6 , Et 3 N·3HF, Et 4 NBF 4 , Me 4 NOAc, n Bu 4 NOAc; The solvent is selected from any one or more than two of water, dichloroethane, methanol, ethanol, tetrahydrofuran and dichloromethane.
  4. 4. The process for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein the reaction equation of the alkoxycarbonyl reaction is:
  5. 5. The method for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein the molar ratio of the non-cyclic alkylamide compound, methyl hydrazinoformate, electrolyte and additive is 1.0 to 5.0 to 0.5.0 to 1.0 and the initial concentration of the non-cyclic alkylamide compound is 0.02 to 0.2 mol/L.
  6. 6. The method for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein the electrochemical reaction is conducted under a constant current condition with an energizing current of 5-15 mA, wherein the electrochemical reaction is conducted without separating an electrolytic cell from a DC regulated power supply.
  7. 7. The method for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein the positive electrode is selected from any one of a carbon sheet, a carbon cloth, a graphite felt, a platinum sheet, a carbon rod, etc., and the negative electrode is selected from any one of a platinum sheet, a stainless steel sheet, a nickel sheet, a carbon sheet, etc.
  8. 8. The process for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein the alkoxycarbonylating reaction temperature is 20 to 100 0 C and the reaction time is 2 to 10 hours.
  9. 9. The method for producing an enamide skeleton (E) -alkoxycarbonyl derivative according to claim 3, wherein said alkoxycarbonylating reaction is followed by separation and purification by any one of column chromatography, liquid chromatography, distillation and recrystallization.

Description

Alkene-containing amide skeleton (E) -alkoxycarbonyl derivative and preparation method thereof Technical Field The invention relates to the technical field of organic synthesis, in particular to an enamide skeleton-containing (E) -alkoxycarbonyl derivative and a preparation method thereof. Background Among the various methods of constructing the C-C bond, carbonylation reactions are a powerful synthetic tool. In particular, alkoxycarbonyl has high value because it can directly introduce ester groups into organic molecules. The direct insertion of the ester functionality into the organic backbone provides a more efficient and direct strategy than classical carboxylic acid esterification. On the other hand, enamide compounds are widely used for synthesizing a plurality of chiral amines and nitrogen-containing heterocyclic compounds as important synthetic building blocks in organic synthesis. The direct functionalization of enamides by β -C (sp 2) -H is an effective strategy for constructing functionalized enamide derivatives, and thus, a series of important research results have been achieved. However, there are relatively few reports on the synthesis of β -alkoxycarbonylated enamide derivatives. In 2014, loh group reported that the first iron catalyzed alkoxycarbonylating reaction of enamide beta-C (sp 2) -H, which has better stereoselectivity, mainly produced Z-beta-alkoxycarbonylated enamide derivatives, but required the use of additional peroxide and metal catalyst. Therefore, the development of an environment-friendly and efficient method for synthesizing the E-type beta-alkoxycarbonyl enamide derivative has good scientific significance and application value. In recent years, electrochemical organic synthesis is used as a high-efficiency green synthesis method, weak current is used for replacing the traditional chemical oxidation or reduction reagent, the use of toxic or expensive metal reagent can be effectively avoided, the pollution of the synthesis process to the environment is reduced, the advantages in the green chemical field are obvious, and the electrochemical organic synthesis method has been widely used in organic synthesis reactions. However, literature studies have shown that methods for synthesizing β -alkoxycarbonylated enamide derivatives based on electrochemical oxidation have not been reported. Disclosure of Invention The invention provides an enamide skeleton-containing (E) -alkoxycarbonyl derivative and a preparation method thereof. beta-C (sp 2) -H alkoxycarbonyl reaction of electrocatalytic non-cyclic acrylamide and methyl hydrazinoformate is used to synthesize E-beta-alkoxycarbonyl derivative containing enamide skeleton. In order to achieve the above object, the technical scheme of the present invention is as follows: An enamide skeleton-containing (E) -alkoxycarbonyl derivative has the molecular structure as follows: ; Wherein R 1 is phenyl, alkyl, alkoxy, halogen or thiomethyl, R 2 is benzyl, methyl, acyl or tert-butoxycarbonyl, and R 3 is alkyl. As an improvement to the above technical scheme, the enamide skeleton-containing (E) -alkoxycarbonyl derivative comprises: 。 As an improvement to the technical scheme, the invention provides a preparation method for preparing the (E) -alkoxycarbonyl derivatives containing the enamide skeleton, which comprises the following steps: In a reactor equipped with an electrode sheet, a non-cyclic alkylamide compound, hydrazino formate, an additive, an electrolyte and a solvent are mixed, and beta-C (sp 2) -H alkoxycarbonyl reaction is carried out under electrochemical conditions, so that a series E-type beta-alkoxycarbonyl enamide derivative is obtained with high selectivity. As an improvement to the technical scheme, the reactor provided with the electrode plates is an electrolytic tank which is not separated, the power supply is a direct-current stabilized power supply, the reaction is carried out under the condition of constant current, and the electrified current is 5-15 milliamperes. More preferably 10 milliamps. As an improvement to the technical scheme, the positive electrode of the reactor provided with the electrode sheet is selected from any one of a carbon sheet, a carbon cloth, a graphite felt, a platinum sheet, a carbon rod and the like, and the negative electrode is selected from any one of a platinum sheet, a stainless steel sheet, a nickel sheet, a carbon sheet and the like. Preferably graphite felt anode and platinum sheet as cathode. As an improvement on the technical scheme, the non-cyclic alkylamide compound has the following structure: 。 as an improvement to the above technical scheme, the hydrazinoformate has the following structure: 。 As an improvement of the above technical scheme, the additive is selected from any one or more of nitric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, potassium carbonate, potassium bicarbonate and sodium acetate, and is mixed in any ratio. Trifluoroacetic acid is preferred as a