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Quaternary carbon center full-substituted pyridine compound and preparation method thereof

A fully substituted, compound technology, applied in the field of fully substituted pyridine compounds and their preparation, can solve problems such as scarcity of methods, and achieve the effects of low cost, wide substrate range, and mild reaction conditions

Active Publication Date: 2020-09-11
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In organic synthesis methodology, the synthesis of pyridine derivatives at the α-position chiral center has certain challenges because pyridine compounds will poison the catalyst during the reaction process. So far, the reported methods are relatively rare, and most methods require the use of Prefunctionalized pyridine compounds as starting materials

Method used

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  • Quaternary carbon center full-substituted pyridine compound and preparation method thereof
  • Quaternary carbon center full-substituted pyridine compound and preparation method thereof
  • Quaternary carbon center full-substituted pyridine compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Embodiment 1: With 2-phenyl-2-(4-phenylbutynyl) malononitrile 1a and 6-dodecyne as standard substrates, to the reaction of the fully substituted pyridine compound of synthetic α-cyano quaternary carbon center Ligand research in:

[0035]

[0036]

[0037] entry ligand yield(%) ee(%) 1 L1 36 50 2 L2 70 50 3 L3 51 66 4 L4 57 40 5 L5 75 30 6 L6 51 60 7 L7 79 34 8 L8 57 48 9 L9 75 44 10 L10 36 44 11 L11 52 58 12 L12 55 30 13 L13 56 60 14 L14 21 50 15 L15 11 5

[0038] At 65 degrees Celsius, react in 1mL 1,4-dioxane solvent for 24 hours; wherein bis(1,5-cyclooctadiene) nickel is a nickel complex; the ligand structure is shown as L1-L15; mol % refers to the relative molar weight, equiv represents the equivalent; yield refers to the total NMR yield of the fully substituted pyridine compound containing α-cyano quaternary carbon center, with s-trimeth...

Embodiment 2

[0039] Embodiment 2: With 2-phenyl-2-(4-phenylbutynyl) malononitrile 1a and 6-dodecyne as standard substrates, nickel-catalyzed synthesis of fully substituted pyridines with α-cyano quaternary carbon centers Research on solvents in compound reactions:

[0040]

[0041]

[0042] Under 65 degrees centigrade, react in the solvent shown in 1mL form for 24 hours; Wherein bis(1,5-cyclooctadiene) nickel is a nickel complex; Ligand structure is as shown in L3; mol% refers to the relative molar weight, Equiv stands for equivalent; yield refers to the total NMR yield of fully substituted pyridine compounds containing α-cyanoquaternary carbon chiral centers, with s-trimethoxybenzene as the internal standard. ee refers to the enantioselectivity of fully substituted pyridine compounds containing α-cyanoquaternary carbon chiral centers, determined by HPLC; where 1,4-dioxane refers to 1,4-dioxane, THF refers to tetrahydrofuran , 2-MeTHF refers to 2-methyltetrahydrofuran, MTBE refers t...

Embodiment 3

[0043] Example 3: With 2-phenyl-2-(4-phenylbutynyl) malononitrile 1a and 6-dodedecyne as standard substrates, nickel-catalyzed synthesis of fully substituted pyridines with α-cyano quaternary carbon centers Research on the molecular sieve type, concentration and temperature, and the amount of alkynes in the compound reaction:

[0044]

[0045]

[0046] At 65 degrees Celsius, react in 1mL 2-methyltetrahydrofuran solvent for 24 hours; wherein bis(1,5-cyclooctadiene) nickel is a nickel complex; the ligand structure is shown in L3; mol% refers to the relative mole Quantity, equiv stands for equivalent; yield refers to the total NMR yield of fully substituted pyridine compounds containing α-cyano quaternary carbon centers, with s-trimethoxybenzene as the internal standard. ee refers to the enantioselectivity of fully substituted pyridine compounds containing α-cyano quaternary carbon centers, determined by high performance liquid chromatography. a 3 equivalents of 6-dodedecy...

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Abstract

The invention provides a quaternary carbon center full-substituted pyridine compound and a preparation method thereof. Alkyne and a high propargyl substituted disubstituted malononitrile compound aresubjected to [2 + 2 + 2] cycloaddition reaction under the catalysis of metal nickel. According to the preparation method, a cheap nickel metal catalyst is selected, a pyridine ring is constructed in one step through two-component reaction, and the malononitrile derivative is desymmetrically constructed to construct chirality, so that the preparation method has the characteristics of low cost, readily available raw materials, mild reaction conditions, good enantioselectivity and the like. The invention also provides a preparation method of C2 symmetrical spiropyridine compound V. The prepared cyano-substituted full-substituted pyridine compound and the C2-symmetric spiropyridine compound are widely applied to the fields of organic synthesis, medicinal chemistry and materials.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a fully substituted pyridine compound with a quaternary carbon center and a preparation method thereof. Background technique [0002] Fully substituted pyridine derivatives are a very important class of heterocyclic compounds. They are not only the basic core skeletons of many natural products, drug molecules and bioactive molecules, but also play a very important role in the field of pesticide chemistry. Because this kind of all-substituted pyridine compound has important potential application value, it is of great significance to synthesize this kind of compound. So far, although many literatures have reported the research methods of synthesizing these compounds, the further development of their synthetic methods is still a hot spot in the field of organic synthesis. [0003] In organic synthesis methodology, the synthesis of pyridine derivatives at the α-position ch...

Claims

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Application Information

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IPC IPC(8): C07D471/10C07D221/04C07D409/04C07D409/06C07D405/06C07D403/06C07F7/08
CPCC07B2200/07C07D221/04C07D403/06C07D405/06C07D409/04C07D409/06C07D471/10C07F7/0814C07F7/083
Inventor 刘文博蔡进辉
Owner WUHAN UNIV