A class of nitrogen bismuth octylcycloalkyl bismuth compounds and their synthesis method

Abstract

The present invention discloses a method for synthesizing a novel nitrogen-bismuth octane bismuth alkyl compound. The synthesis method is carried out by reacting nitrogen-bismuth octane organic bismuth chloride with an alkyl halide in the presence of ferric phosphate as a catalyst, 2,2-bipyridine as a ligand, manganese as a reducing agent, lithium chloride as an additive, DMF as a solvent, and a temperature of 100°C. The reaction can be completed in a relatively short time (3 hours), has good functional group tolerance, and has a high yield. Considering its sp 3 Organic bismuth compounds with carbon-bismuth bonds can be used to construct sp 3 It can also be widely used in carbon-carbon bond coupling reactions and the synthesis of drugs and natural products.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a class of nitrogen bismuth octylcycloalkyl bismuth compounds and a synthesis method thereof. Background Art

[0002] Transition-metal-catalyzed reductive coupling reactions involve the coupling of two electrophilic reagents in the presence of a transition metal catalyst and a reducing agent. Due to their advantages such as step economy, chemoselectivity, and wide substrate functional group compatibility, these reactions have been widely used in the synthesis of fine chemicals, pharmaceuticals, agrochemicals, multifunctional organic molecules, and complex natural products. Organometallic reagents, as the most commonly used coupling reagents for constructing carbon-carbon and carbon-hetero bonds, have been extensively studied. However, most known organometallic reagents, such as organolithium reagents, Grignard reagents, and organozinc reagents, are sensitive to water and oxygen, as well as exhibit poor functional group tolerance, which limits their further application. Nitrogen-bismuth octane ring organobismuth halides possess unique advantages in water and oxygen resistance. Combining the advantages of reductive coupling reactions with these advantages of nitrogen-bismuth octane ring organobismuth halides has enabled the synthesis of a class of water- and oxygen-resistant organobismuth alkyl coupling reagents, making them widely applicable alkylating agents. Summary of the Invention

[0003] The present invention discloses a method for synthesizing nitrogen-bismuth-octane-cycloalkyl bismuth compounds. This method uses nitrogen-bismuth-octane-cycloorganobismuth chloride and a haloalkane as reactants, and N,N-dimethylformamide as solvent, to synthesize a series of novel nitrogen-bismuth-octane-cycloalkyl bismuth compounds at 100°C. The reaction can be carried out at 100°C within 3 hours with moderate to high yields. This synthesis method has the advantages of mild conditions, fast reaction speed, high yield, ease of operation, and scalability, making it suitable for industrial production.

[0004] In order to achieve a rapid reaction under mild conditions and then conduct transformation and application experiments, it is essential to explore the reaction mechanism. Through relevant control experiments, we proposed two possible reaction pathways. Pathway 1: (1) Alkyl halide forms an alkyl manganese reagent under the action of manganese and lithium chloride; (2) The alkyl manganese reagent directly reacts with organic bismuth chloride to obtain the target product. Pathway 2: (1) The iron catalyst is reduced to +1 valence under the action of manganese and oxidatively adds with the alkyl halide to obtain intermediate A; (2) Intermediate A is reduced to monovalent iron B by manganese, and B oxidatively adds with 1a to obtain trivalent iron complex C; (3) C undergoes reduction elimination to obtain the target product, and at the same time, iron is reduced to +1 valence and re-enters the cycle.

[0005]

[0006] In the above synthesis method, the synthesis method of the raw material nitrogen-bismuth octyl ring organic bismuth chloride 1a is as follows:

[0007]

[0008] In the above synthesis method, nitrogen-bismuth octane ring organic bismuth chloride and halogenated alkane are used as raw materials, N,N-dimethylformamide is used as solvent, and the reaction is carried out at a temperature of 100° C. under a nitrogen atmosphere for 12 hours.

[0009] A series of nitrogen-bismuth octane bismuth alkyl compounds were synthesized using this synthesis method, wherein the product structures are as follows:

[0010]

[0011] The nitrogen-bismuth octane ring bismuth alkyl synthesis method is characterized by using nitrogen-bismuth octane ring organic bismuth chloride 1a (0.2 mmol) and alkyl halide 2 (0.3 mmol) as raw materials, iron phosphate (5 mol%) as a catalyst, 2,2-bipyridine (5 mol%) as a ligand, 2.0 equivalents of manganese as a reducing agent, and 2.0 equivalents of lithium chloride as an additive. Under a nitrogen atmosphere, the reaction is carried out at 100° C. for 3 hours to obtain nitrogen-bismuth octane ring bismuth alkyl compounds 3a-3ab with a yield of 10-87%. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 Schematic diagram of the reaction principle of the present invention. DETAILED DESCRIPTION

[0013] To make the above-mentioned features, advantages, and purposes of the present invention more clearly understood, the present invention is described in detail below in conjunction with specific embodiments. The above description sets forth many specific details to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar modifications without violating the scope of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0014] Unless otherwise specified, the reaction raw materials and catalysts involved in the following examples are conventional commercially available reagents on the market.

[0015] Preparation Examples 1-28 of Nitrogen-Bismuth Octyl Ring Bismuth Alkyl Compounds

[0016] Example 1

[0017] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2a, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The mixture was reacted at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 43% yield.

[0018] The structural characterization of internal alkyne compound 3a is as follows:

[0019] 1 H NMR (400MHz, CDCl3) δ7.86 (d, J=6.9Hz, 1H), 7.26 (dd, J=12.3, 4.2Hz, 1H), 7.20 (dd,J=8.5,7.0Hz,1H),6.97(d,J=8.2Hz,1H),6.88–6.81(m,1H),4.64(d,J=15.0Hz,1H), 4.31(d,J=14.9Hz,1H),2.25–2.17(m,1H),2.03(ddd,J=16.4,11.5,6.9Hz,1H),1.54–1.49 (m,1H),1.03–0.94(m,2H).

[0020] 13 C NMR (101MHz, CDCl3) δ149.2,145.2,144.6,136.6,129.3,128.9,127.9,127.5,119.9, 115.9,58.2,35.8,30.7,28.5,14.0.

[0021] Example 2

[0022] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 0.3 mmol of alkyl halide 2b, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The mixture was reacted at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in a 73% yield.

[0023] Example 3

[0024] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2c, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 47% yield.

[0025] Example 4

[0026] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2d, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in an 87% yield.

[0027] Example 5

[0028] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2e, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 36% yield.

[0029] Example 6

[0030] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2f, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The mixture was reacted at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 38% yield.

[0031] Example 7

[0032] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 2 g (0.3 mmol) of alkyl halide, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in a 68% yield.

[0033] Example 8

[0034] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2h, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 48% yield.

[0035] Example 9

[0036] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2i, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 51% yield.

[0037] Example 10

[0038] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2j, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 74% yield.

[0039] Example 11

[0040] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 0.3 mmol of alkyl halide 2k, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in a 60% yield.

[0041] Example 12

[0042] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2l, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 50% yield.

[0043] Example 13

[0044] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2m, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 25% yield.

[0045] Example 14

[0046] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2n, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 48% yield.

[0047] Example 15

[0048] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2o, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 51% yield.

[0049] Example 16

[0050] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 0.3 mmol of alkyl halide 2p, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was carried out at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in an 87% yield.

[0051] Example 17

[0052] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 0.3 mmol of alkyl halide 2q, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in a 65% yield.

[0053] Example 18

[0054] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2r, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 74% yield.

[0055] Example 19

[0056] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2s, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 59% yield.

[0057] Example 20

[0058] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2t, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 41% yield.

[0059] Example 21

[0060] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2u, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in an 80% yield.

[0061] Example 22

[0062] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2v, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 52% yield.

[0063] Example 23

[0064] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2w, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 10% yield.

[0065] Example 24

[0066] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2x, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The mixture was reacted at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 54% yield.

[0067] Example 25

[0068] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2y, 0.02 mmol of ferric phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 34% yield.

[0069] Example 26

[0070] In a 10 mL reaction tube, 0.2 mmol of nitrogen-bismuth octyl ring organobismuth chloride 1a, 0.3 mmol of alkyl halide 2z, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride were added. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octyl ring bismuth alkyl compound was isolated by column chromatography as a white solid in an 80% yield.

[0071] Example 27

[0072] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2aa, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After completion of the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 19% yield.

[0073] Example 28

[0074] To a 10 mL reaction tube, add 0.2 mmol of nitrogen-bismuth octane organobismuth chloride 1a, 0.3 mmol of alkyl halide 2ab, 0.02 mmol of iron phosphate, 0.02 mmol of 2,2-bipyridine, 0.4 mmol of manganese powder, and 0.4 mmol of lithium chloride. The reaction was incubated at 100°C under a nitrogen atmosphere for 3 hours. After the reaction, the nitrogen-bismuth octane organobismuth chloride was isolated by column chromatography as a white solid in a 69% yield.

[0075] The above-described embodiments merely represent several implementations of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous modifications and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the appended claims.

Claims

1. A method for synthesizing a class of alkyl bismuth nitrogen bismuth octyl ring organic bismuth derivatives 3, characterized in that: The method uses nitrogen-bismuth octane ring organic bismuth chloride 1a and alkyl halide hydrocarbon 2 as raw materials; iron phosphate as a catalyst, the amount of which is 5-20%; manganese as a reducing agent, the amount of which is 1-2.5 equivalents; anhydrous lithium chloride as an additive; bipyridine as a ligand, the amount of which is 0.1 equivalents; N,N-dimethylformamide as a solvent, and reacts at 80°C, 90°C or 100°C to obtain alkyl bismuth nitrogen-bismuth octane ring organic bismuth derivative 3. Among them, the chemical structure of nitrogen bismuth octyl ring bismuth halide 1a is: The chemical formula of alkyl halide 2 is: Alkyl-X; The chemical structure of the alkyl bismuth nitrogen bismuth octyl ring organic bismuth derivative 3 is: Wherein, the substituent Alkyl is n-butyl, n-pentyl, n-hexyl, n-heptyl, n-dodecyl, n-octadecyl, 4-pentenyl, 3-butynyl, 3-(dimethoxymethyl)propyl, 4-methoxybutyl, 4-carbonylpentyl, 4-cyanopentyl, 2-ethoxycarbonylethyl, 3-(dimethyl-tert-butylsilyloxy)propyl, 3-trifluoromethylpropyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 2-(6-benzotetrahydrofuran)ethyl, 2 -(4-fluorophenyl)ethyl, 4-(4-methoxyphenoxy)butyl, 4-(4-bromophenoxy)butyl, 4-(4-cyanophenoxy)butyl, 4-(4-formylphenoxy)butyl, 4-(N-carbazolyl)butyl, 4-(3-tert-butylphenoxy)butyl, 6-(4-(N,N-dipropylaminosulfonyl)benzoic acid hexyl and 5-benzo[d][1,3]dioxolaneoxybutyl; X is one of Cl, Br and I.

2. The method for synthesizing the alkyl bismuth nitrogen bismuth octyl ring organic bismuth derivative 3 according to claim 1, characterized in that: The reaction temperature was 100°C.

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