Synthesis method of N-formamide derivative

Abstract

The invention discloses a synthesis method of an N-formamide derivative, and belongs to the technical field of chemical synthesis, the N-formamide derivative is obtained by a one-step method by taking an isonitrile compound as a substrate and a titanocene compound as a catalyst and carrying out hydrolysis reaction in an organic solvent at room temperature and normal pressure. According to the method, the titanocene compound is used as a catalyst, and the hydrolysis reaction is selectively terminated to the step of generating the formamide compound in the isonitrile compound hydrolysis process, so that the isonitrile compound is prevented from being further hydrolyzed to generate the amine compound. The method has the advantages of simple reaction process, cheap and easily available reaction system, wide substrate range, mild reaction conditions, high target product yield and no burden on the environment.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing N-formamide derivatives. Background Art

[0002] Formamide and its derivatives have active reactivity and special solubility. They can be used as raw materials for organic synthesis and have many uses in pesticides, dyes, pigments, fragrances, and additives.

[0003] The traditional method for synthesizing formamide is to directly generate formamide from nitroaromatic hydrocarbons, for example, nitroaromatic hydrocarbons and formic acid generate formamide, but formic acid is highly corrosive and will pollute the environment. Formamide is generated by amines in the presence of O2, CO, or CO2. For example, Dai's team used O2 to react with amines to generate formamide, but O2 supports combustion and can easily cause fires. Li's team used amines to react with CO to generate formamide, but CO is toxic and can endanger life safety. Fang's team used amines to react with CO2 to generate formamide, but excessive CO2 emissions can cause a greenhouse effect. Based on the environmental and safety issues of the above-mentioned traditional preparation of formamide derivatives, researchers are in urgent need of exploring a greener method for synthesizing formamide derivatives.

[0004] Reactions that hydrolyze isonitrile compounds to form N-formamide are typically performed in strongly acidic aqueous solutions. For example, in 2005, A. Porcheddu's team demonstrated that the hydrolysis of isonitriles requires strong acid. In 2004, J.S. Simpson's team and in 2011, H. Prawat's team discovered that the conversion of isonitriles to formamide requires acetic acid or trifluoroacetic acid. In 2010, D. Zhang's team discovered that the hydrolysis of isonitriles requires a water-1,4-dioxane system and hydrochloric acid. All of these reactions require high temperatures. Strongly acidic aqueous solutions are highly corrosive, making them dangerous to operate and requiring high-quality, corrosion-resistant materials for the reaction equipment, increasing equipment cost and maintenance difficulties. The water-1,4-dioxane system has certain toxicity and environmental impacts, and high-temperature reactions can produce byproducts that affect product purity. Summary of the Invention

[0005] The present invention provides a method for synthesizing N-formamide derivatives, which effectively solves the pollution and safety problems existing in the traditional synthesis of formamide derivatives. The existing synthesis of formamide derivatives using isonitrile compounds as substrates requires a strong acid environment, the existing reaction system is toxic, and high temperature leads to the generation of by-products, thereby affecting the purity of the product. At the same time, a method for synthesizing formamide derivatives is provided, which has cheap and readily available reaction raw materials, a wide substrate range, mild reaction conditions, and a high yield of the target product.

[0006] The object of the present invention is to provide a method for synthesizing N-formamide derivatives, comprising the following steps:

[0007] Using the isonitrile compound of formula 1 as a substrate and a titanocene compound as a catalyst, a hydrolysis reaction is carried out in an organic solvent at room temperature and normal pressure to obtain an N-formamide derivative of formula 2 in one step. The synthetic route is: Wherein, R is selected from phenyl, substituted phenyl, biphenyl, or a substituted biphenyl group.

[0008] As a preferred embodiment, the substituent of the substituted phenyl group is an alkyl group, a halogen group, an alkoxy group, a naphthyl group or a thienyl group; the substituent of the substituted biphenyl group is an alkoxy group, a halogen group, an acetoxy group, a sulfur atom or a cyano group.

[0009] As a preferred embodiment, the alkyl group is a C1-C4 alkyl group, and the alkoxy group is a C1-C4 alkoxy group.

[0010] As a preferred embodiment, the isonitrile compound is 1-isocyanato-4-methylbenzene 1-Iodo-4-isocyanobenzene 1-Isocyano-2-methylbenzene 1-(tert-Butyl)-4-isocyanobenzene 1-Isocyano-4-methoxybenzene 2-Isocyano-1,1'-biphenyl 2-Isocyano-4'-methoxy-1,1'-biphenyl (4-Isocyanophenyl)(phenyl)methanone 3',4'-difluoro-2-isocyanato-1,1'-biphenyl 2'-Isocyano-[1,1'-biphenyl]-4-carboxylic acid methyl ester (2'-Isocyano-[1,1'-biphenyl]-4-yl)(methyl)sulfur 4'-Chloro-2-isocyanato-1,1'-biphenyl 2-(3-Isocyanophenyl)naphthalene 2-(2-isocyanophenyl)thiophene or 2'-isocyano-[1,1'-biphenyl]-4-carbonitrile

[0011] As a preferred embodiment, the titanocene compound is cyclopentadienyltrichlorotitancene, pentamethylcyclopentadienyltrichlorotitancene or trichlorotitancene.

[0012] As a preferred embodiment, the molar ratio of the isonitrile compound to the titanocene compound is 1:0.5-1.

[0013] As a preferred embodiment, the reaction time is 1 h to 12 h.

[0014] As a preferred embodiment, after the hydrolysis reaction is stopped, a mixture is obtained, and the mixture is filtered through a silica gel pad and purified by column chromatography using n-hexane and ethyl acetate as eluents to obtain N-formamide derivatives.

[0015] As a preferred embodiment, the organic solvent is dichloromethane or tetrahydrofuran.

[0016] As a preferred embodiment, the N-formamide derivative is:

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention provides a method for synthesizing N-formamide derivatives. Using an isonitrile compound as a substrate and a titanocene compound as a catalyst, a hydrolysis reaction is carried out in an organic solvent at room temperature and atmospheric pressure to produce the N-formamide derivatives in a one-step process. The titanocene compound is used as a catalyst to selectively terminate the hydrolysis of the isonitrile compound at the step of forming the formamide compound, thereby preventing the isonitrile compound from further hydrolyzing to form an amine compound. The present invention has a simple reaction process, an inexpensive and readily available reaction system, a wide substrate range, mild reaction conditions, a high yield of the target product, and no environmental impact. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the hydrogen spectrum prepared in Example 1 of the present invention.

[0020] Figure 2 This is the carbon spectrum prepared in Example 1 of the present invention.

[0021] Figure 3 This is the hydrogen spectrum prepared in Example 2 of the present invention.

[0022] Figure 4 This is the carbon spectrum prepared in Example 2 of the present invention.

[0023] Figure 5 This is the hydrogen spectrum prepared in Example 3 of the present invention.

[0024] Figure 6 This is the carbon spectrum prepared in Example 3 of the present invention.

[0025] Figure 7This is the hydrogen spectrum prepared in Example 4 of the present invention.

[0026] Figure 8 This is the carbon spectrum prepared in Example 4 of the present invention.

[0027] Figure 9 This is the hydrogen spectrum prepared in Example 6 of the present invention.

[0028] Figure 10 This is the carbon spectrum prepared in Example 6 of the present invention.

[0029] Figure 11 This is the hydrogen spectrum prepared in Example 7 of the present invention.

[0030] Figure 12 This is the carbon spectrum prepared in Example 7 of the present invention.

[0031] Figure 13 This is the hydrogen spectrum prepared in Example 8 of the present invention.

[0032] Figure 14 This is the carbon spectrum prepared in Example 8 of the present invention.

[0033] Figure 15 This is the hydrogen spectrum prepared in Example 9 of the present invention.

[0034] Figure 16 This is the carbon spectrum prepared in Example 9 of the present invention.

[0035] Figure 17 This is the hydrogen spectrum prepared in Example 10 of the present invention.

[0036] Figure 18 This is the carbon spectrum prepared in Example 10 of the present invention.

[0037] Figure 19 This is the hydrogen spectrum prepared in Example 11 of the present invention.

[0038] Figure 20 This is the carbon spectrum of Example 11 of the present invention.

[0039] Figure 21 This is the hydrogen spectrum prepared in Example 13 of the present invention.

[0040] Figure 22 This is the carbon spectrum of Example 13 of the present invention.

[0041] Figure 23 This is the hydrogen spectrum prepared in Example 14 of the present invention.

[0042] Figure 24 This is the carbon spectrum of Example 14 of the present invention.

[0043] Figure 25This is the hydrogen spectrum prepared in Example 15 of the present invention.

[0044] Figure 26 This is the carbon spectrum of Example 15 of the present invention. DETAILED DESCRIPTION

[0045] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention is further described below with reference to specific examples, but the examples are not intended to limit the present invention. The following experimental and detection methods are conventional methods unless otherwise specified; the reagents and raw materials are commercially available unless otherwise specified.

[0046] In view of the problems that the existing synthesis methods of formamide derivatives have complicated synthesis steps and harsh reaction conditions, the present invention provides a synthesis method of formamide derivatives using isonitrile compounds as substrates and titanocene compounds as catalysts.

[0047] The technical solution of the present invention is described in detail below.

[0048] The present invention provides a method for synthesizing N-formamide derivatives, comprising the following steps:

[0049] Using the isonitrile compound of formula 1 as a substrate and a titanocene compound as a catalyst, a hydrolysis reaction is carried out in an organic solvent at room temperature and normal pressure to obtain an N-formamide derivative of formula 2 in one step. The synthetic route is: Wherein, R is selected from phenyl, substituted phenyl, biphenyl, or a substituted biphenyl group.

[0050] In the prior art, hydrolysis reactions using isonitrile compounds as substrates typically produce amine compounds. However, the present invention uses a titanocene compound as a catalyst to selectively terminate the hydrolysis reaction during the hydrolysis of isonitrile compounds to produce formamide compounds without producing amine compounds. The present invention, using a titanocene compound as a catalyst, can promote the reaction of isonitrile compounds containing different substituents to produce corresponding N-formamide derivatives, achieving outstanding results. The present invention can react at room temperature and pressure, produces no by-products, has a high yield, does not require special equipment, is simple to operate, and allows for simple separation and purification.

[0051] In order to further illustrate the technical effect of the present invention, the isonitrile compound used in the present invention is selected from 1-isocyanato-4-methylbenzene 1-Iodo-4-isocyanobenzene 1-Isocyano-2-methylbenzene 1-(tert-Butyl)-4-isocyanobenzene 1-Isocyano-4-methoxybenzene 2-Isocyano-1,1'-biphenyl 2-Isocyano-4'-methoxy-1,1'-biphenyl (4-Isocyanophenyl)(phenyl)methanone 3',4'-difluoro-2-isocyanato-1,1'-biphenyl 2'-Isocyano-[1,1'-biphenyl]-4-carboxylic acid methyl ester (2'-Isocyano-[1,1'-biphenyl]-4-yl)(methyl)sulfur 4'-Chloro-2-isocyanato-1,1'-biphenyl 2-(3-Isocyanophenyl)naphthalene 2-(2-isocyanophenyl)thiophene or 2'-isocyano-[1,1'-biphenyl]-4-carbonitrile

[0052] In order to hydrolyze isonitrile compounds to synthesize corresponding N-formamide derivatives, the titanocene compound used in the present invention is cyclopentadienyl trichloro-titanocenes, pentamethylcyclopentadienyl trichloro-titanocenes or trichloro-titanocenes.

[0053] In order to further improve the yield and purity of N-formamide derivatives, the molar ratio of the isonitrile compound to the titanocene compound is 1:0.5-1.

[0054] In order to control the yield and purity of the reaction product, the reaction time is 1 h to 12 h.

[0055] It should be noted that after the hydrolysis reaction is stopped, a mixture is obtained, which is filtered through a silica gel pad and purified by column chromatography using n-hexane and ethyl acetate as eluents to obtain N-formamide derivatives.

[0056] The organic solvent used in the present invention is an ultra-dry solvent, and the organic solvent is dichloromethane.

[0057] The present invention will now be further described with reference to specific embodiments.

[0058] 1. Synthesis process of N-formamide derivatives of the present invention

[0059] Synthesis of N-formamide derivatives: Using the isonitrile compound of formula 1 as a substrate and a titanocene compound as a catalyst, a hydrolysis reaction is carried out in an organic solvent at room temperature and normal pressure to obtain the N-formamide derivative of formula 2 in one step. The synthetic route is: Wherein, R is selected from aryl, substituted aryl or substituted heterocyclic aryl.

[0060] 2. The present invention synthesized the following 15 N-formamide derivatives:

[0061] The specific preparation steps and specific structural formulas of the 15 N-formamide derivatives of Examples 1 to 15 are as follows.

[0062] 1. The specific preparation steps of the derivative of the structural formula of Example 1 are as follows:

[0063] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0234 g (0.2 mmol) of 1-isocyano-4-methylbenzene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-toluamide (21.6 mg). Its structural formula is The yield was 80%.

[0064] 2. The specific preparation steps of the derivative of the structural formula of Example 2 are as follows:

[0065] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0458 g (0.2 mmol) of 1-iodo-4-isocyanobenzene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4-iodophenyl)formamide (32.1 mg), the structural formula of which is The yield was 65%.

[0066] 3. The specific preparation steps of the derivative of the structural formula of Example 3 are as follows:

[0067] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0234 g (0.2 mmol) of 1-isocyanato-2-methylbenzene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain NO-toluamide (23.8 mg), the structural formula of which is The yield was 88%.

[0068] 4. The specific preparation steps of the derivative of the structural formula of Example 4 are as follows:

[0069] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0319 g (0.2 mmol) of 1-(tert-butyl)-4-isocyanobenzene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4-(tert-butyl)phenyl)formamide (15.2 mg), the structural formula of which is The yield was 43%.

[0070] 5. The specific preparation steps of the derivative of the structural formula of Example 5 are as follows:

[0071] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0319 g (0.2 mmol) of 1-isocyano-4-methoxybenzene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4-methoxyphenyl)formamide (12.7 mg). Its structural formula is The yield was 42%.

[0072] 6. The specific preparation steps of the derivative of the structural formula of Example 6 are:

[0073] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0358 g (0.2 mmol) of 2-isocyano-1,1'-biphenyl, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-([1,1'-biphenyl]-2-yl)formamide (32.4 mg), the structural formula of which is The yield was 82%.

[0074] 7. The specific preparation steps of the derivative of the structural formula of Example 7 are:

[0075] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0419 g (0.2 mmol) of 2-isocyano-4'-methoxy-1,1'-biphenyl, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4'-methoxy-[1,1'-biphenyl]-2-yl)formamide (40 mg), the structural formula of which is The yield was 88%.

[0076] 8. The specific preparation steps of the derivative of the structural formula of Example 8 are:

[0077] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0415 g (0.2 mmol) (4-isocyanophenyl) (phenyl)methanone, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 hours. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4-benzoylphenyl)formamide (33.8 mg). Its structural formula is: The yield was 75%.

[0078] 9. The specific preparation steps of the derivative of the structural formula of Example 9 are as follows:

[0079] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0430 g (0.2 mmol) of 3', 4'-difluoro-2-isocyano-1,1'-biphenyl, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(3', 4'-difluoro-[1,1'-biphenyl]-2-yl)formamide (38.3 mg), the structural formula of which is The yield was 82%.

[0080] 10. The specific preparation steps of the derivative of the structural formula of Example 10 are:

[0081] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0475 g (0.2 mmol) of 2'-isocyano-[1,1'-biphenyl]-4-carboxylic acid methyl ester, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain 2'-formamido-[1,1'-biphenyl]-4-carboxylic acid methyl ester (49 mg). Its structural formula is The yield was 96%.

[0082] 11. The specific preparation steps of the derivative of the structural formula of Example 11 are:

[0083] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0451 g (0.2 mmol) of (2'-isocyano-[1,1'-biphenyl]-4-yl)(methyl)sulfur, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4'-(methylthio)-[1,1'-biphenyl]-2-yl)formamide (33.6 mg), the structural formula of which is The yield was 69%.

[0084] 12. The specific preparation steps of the derivative of the structural formula of Example 12 are:

[0085] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0426 g (0.2 mmol) of 4'-chloro-2-isocyanate-1,1'-biphenyl, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4'-chloro-[1,1'-biphenyl]-2-yl)formamide (19 mg), the structural formula of which is The yield was 41%.

[0086] 13. The specific preparation steps of the derivative of the structural formula of Example 13 are:

[0087] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0459 g (0.2 mmol) of 2-(3-isocyanophenyl)naphthalene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(3-(naphthalene-2-yl)phenyl)formamide (43 mg), the structural formula of which is The yield was 87%.

[0088] 14. The specific preparation steps of the derivative of the structural formula of Example 14 are:

[0089] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0459 g (0.2 mmol) of 2-(2-isocyanophenyl)thiophene, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(2-(thiophen-2-yl)phenyl)formamide (35.8 mg), the structural formula of which is The yield was 88%.

[0090] 15. The specific preparation steps of the derivative of the structural formula of Example 15 are:

[0091] At room temperature, 0.0591 g (0.2 mmol) of pentamethylcyclopentadienyltrichloromonocene titanate, 0.0459 g (0.2 mmol) of 2'-isocyano-[1,1'-biphenyl]-4-carbonitrile, and 2 mL of dichloromethane were added to a sealed tube and reacted for 12 h. After the reaction, the reaction mixture was filtered through a silica gel pad and purified by flash column chromatography using n-hexane and ethyl acetate as eluents to obtain N-(4'-cyano-[1,1'-biphenyl]-2-yl)formamide (40 mg), the structural formula of which is The yield was 90%.

[0092] III. The physicochemical parameters and structural parameters of the N-formamide derivatives of the structural formulas of Examples 1 to 15 are shown in Table 2 below.

[0093] Table 2 Physicochemical parameters and structural parameters of 15 N-formamide derivatives

[0094]

[0095]

[0096]

[0097]

[0098] In summary, the present invention utilizes a titanocene compound as a catalyst to selectively terminate the hydrolysis reaction of isonitrile compounds to form formamide compounds without generating amine compounds. The present invention utilizes a titanocene compound as a catalyst to promote the reaction of isonitrile compounds containing various substituents to generate corresponding N-formamide derivatives, achieving outstanding results. The present invention can proceed at room temperature and pressure, produces no by-products, and has a high yield. It does not require special equipment, is simple to operate, and allows for simple separation and purification.

[0099] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A method for synthesizing N-formamide derivatives, characterized in that: The following steps are involved: Using the isonitrile compound of formula 1 as a substrate and a titanocene compound as a catalyst, a hydrolysis reaction is carried out in an organic solvent at room temperature and normal pressure to obtain an N-formamide derivative of formula 2 in one step. The synthetic route is: Wherein, R is selected from phenyl, substituted phenyl, biphenyl, or a substituted biphenyl group.

2. The synthesis method according to claim 1, wherein The substituent of the substituted phenyl group is an alkyl group, a halogen group, an alkoxy group, a naphthyl group or a thienyl group; the substituent of the substituted biphenyl group is an alkoxy group, a halogen group, an acetoxy group, a sulfur atom or a cyano group.

3. The synthesis method according to claim 2, characterized in that The alkyl group is a C1-C4 alkyl group, and the alkoxy group is a C1-C4 alkoxy group.

4. The synthesis method according to claim 1, characterized in that The isonitrile compound is 5. The synthesis method according to claim 1, characterized in that The titanocene compound is cyclopentadienyl trichloro-titanocenes, pentamethylcyclopentadienyl trichloro-titanocenes or trichloro-titanocenes.

6. The synthesis method according to claim 1, characterized in that The molar ratio of the isonitrile compound to the titanocene compound is 1:0.5-1.

7. The synthesis method according to claim 1, characterized in that The reaction time is 1 h to 12 h.

8. The synthesis method according to claim 1, characterized in that After the hydrolysis reaction is stopped, a mixture is obtained, which is filtered through a silica gel pad and purified by column chromatography using n-hexane and ethyl acetate as eluents to obtain N-formamide derivatives.

9. The synthesis method according to claim 1, characterized in that The organic solvent is dichloromethane or tetrahydrofuran.

10. The synthesis method according to claim 1, characterized in that The N-formamide derivatives are:

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