Synthesis method of halogenated biaryl compound

A compound, biaryl technology, applied in the field of synthesis of halogenated biaryl compounds, can solve the problems of harsh reaction conditions, poor selectivity, low yield, etc., to achieve reduced side reactions, high yield, universal substrate sex good effect

Active Publication Date: 2022-07-29
JIANGSU SINOCOMPOUND CATALYST
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Problems solved by technology

[0004] Based on this, it is necessary to provide a method for the preparation of halogenated biaryl compounds, which can effectively improve the harsh conditions of the whole reaction, low yield and low yield of halogenated biaryl compounds in the traditional technology when using C-C bond coupling reaction to prepare halogenated biaryl compounds. The problem of poor selectivity

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  • Synthesis method of halogenated biaryl compound
  • Synthesis method of halogenated biaryl compound
  • Synthesis method of halogenated biaryl compound

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preparation example Construction

[0045] The invention provides a preparation method of a halogenated biaryl compound, which comprises the following steps:

[0046] Under non-reactive gas atmosphere, dihalogenated aryl compound, aryl Grignard reagent, [1,3-bis(2,6-diisopropylbenzene)imidazole-2-idene](3-chloropyridine) Palladium dichloride, alkali and solvent are mixed, and then reacted at 50°C to 75°C;

[0047] The dihalogenated aryl compound has the structure shown in formula I, the aryl Grignard reagent has the structure shown in formula II, and the halogenated biaryl compound has the structure shown in formula III:

[0048]

[0049] wherein each occurrence of X is independently selected from -Br or -I;

[0050] R 1 ~R 9 Each occurrence is independently selected from -H, -D, -NMe 2 , -NO 2 , -CF 3 , halogen, unsubstituted or at least one R 10 substituted C 1 ~C 10 Alkyl or alkoxy, unsubstituted or at least one R 11 substituted C 3 ~C 6 Cycloalkyl, unsubstituted or at least one R 12 substitut...

Embodiment 1

[0081] Under Ar atmosphere, 1,4-dimethoxy-2,3-dibromobenzene (No. 1-4, 30 g, 1.0 eq), Pd-PEPPSI-IPr catalyst (1.38 g, 2 mol%) and t BuONa (14.61 g, 1.5 eq) was stirred at room temperature for 30 min; then 2,4,6-triisopropylbenzenemagnesium bromide Grignard reagent (No. II-8, 1.3 eq) was slowly added, the temperature was raised to 70 °C, TLC monitoring When the reaction is complete, the reaction is stopped and cooled to room temperature;

[0082] 500 mL of water was slowly added to the reaction system, the layers were separated and the organic phase was retained. The aqueous phase was extracted with ethyl acetate (300 mL×3). All organic phases were combined and washed with saturated sodium chloride solution (1 L×1). Dry with sodium sulfate, filter, remove the solvent by distillation under reduced pressure, and purify by column chromatography to obtain the target product No. III-12, which is 37.8 g of white solids, and the yield is 89%.

[0083] III-12 NMR data: 1 H NMR (400 ...

Embodiment 2~20

[0085]Basically the same as Example 1, the difference is that some reaction conditions are different, for example, different catalyst types, different catalyst amounts, different amounts of aryl Grignard reagents, different types of bases, different types of solvents or different reaction temperatures are used. Table 1:

[0086] Table 1

[0087]

[0088] Analyze the data of table 1, as can be known from embodiment 1~5, the selection of Pd-PEPPSI-IPr catalyst has a decisive influence on the smooth occurrence of realization reaction, other common palladium catalyst, or can not react at all (such as embodiment 4) , or the yield is very low. It can be seen from Examples 1, 6 to 9 that with the increase of the catalyst dosage, the reaction yield will also increase, but the increase in the yield becomes very limited when it increases to 3%. It can be seen from Examples 1 and 10-12 that the amount of aryl Grignard reagent will also affect the reaction yield. As the amount increa...

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Abstract

The invention relates to the technical field of organic synthesis, in particular to a synthetic method of a halogenated biaryl compound, which comprises the following steps: in a non-reactive gas atmosphere, mixing a dihalogenated aryl compound, an aryl Grignard reagent, [1, 3-bis (2, 6-diisopropyl benzene) imidazole-2-fork] (3-chloropyridine) palladium dichloride, alkali and a solvent, and reacting at room temperature to obtain the halogenated biaryl compound. And reacting at the temperature of 50-75 DEG C. According to the invention, [1, 3-bis (2, 6-diisopropyl benzene) imidazole-2-fork] (3-chloropyridine) palladium dichloride is specially selected as a catalyst, so that the C-C coupling reaction of the dihalogenated aryl compound and the aryl Grignard reagent can be carried out under the mild condition of 50-75 DEG C, and the harsh condition of-78 DEG C in the traditional technology is not needed; and only a monosubstitution reaction can be carried out with high selectivity, so that the occurrence of side reactions is greatly reduced, and a target product of the halogenated biaryl compound is prepared with a higher yield.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a halogenated biaryl compound. Background technique [0002] The research on the coupling reaction of C-C bond occupies a pivotal position in modern organic synthesis methodology. Since the 20th century, on the basis of existing research, several famous coupling reactions of C-C bonds have been born successively, such as Suzuki Coupling reactions, Heck coupling reactions, Sonogashira coupling reactions, etc., these reactions provide efficient methods for the synthesis of many organic synthesis building blocks. [0003] Halogenated biaryl compounds are an important class of organic synthesis intermediates, which can be used as precursors of compounds such as biaryl phosphine ligands. However, in the traditional technology, when using C-C bond coupling reaction to prepare halogenated biaryl compounds, harsh reaction conditions are often involved...

Claims

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Application Information

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IPC IPC(8): C07C17/263C07C41/30C07C209/68C07C25/18C07C43/225C07C43/29C07C211/52C07B37/04
CPCC07C17/2632C07C41/30C07C209/68C07B37/04C07C25/18C07C43/225C07C43/29C07C211/52
Inventor 陈虎韩露李昌荣
Owner JIANGSU SINOCOMPOUND CATALYST
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