A method for synthesizing organic nitrile compounds from aldehydes

Abstract

The application provides a method for synthesizing organic nitrile compounds from aldehydes, which comprises the following steps: reacting hydroxylamine hydrochloride with aldehyde compounds in acetonitrile as a solvent and trifluoroacetic acid as a reaction aid at room temperature for a certain time to obtain organic nitrile compounds. The method provided by the application avoids the use of strong oxidants and transition metal catalysts, does not need high temperature to promote the reaction, is compatible with air, green, efficient, economical and practical, clean and environmentally friendly, and has a significant advantage in catalytic activity; the method provided by the application uses commercially available hydroxylamine hydrochloride for reaction, has good selectivity, a simple purification process, high yield, and is suitable for various substituent groups (for example, halogen, alcohol, ketone, acid, cyano, heterocycle and the like), and is an easy-to-promote synthesis method.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and in particular relates to a method for synthesizing organic nitrile compounds from aldehydes. Background Technology

[0002] Organic nitriles are important components of pharmaceuticals, agrochemicals, and natural products. The cyanide functional group is a precursor for the synthesis of various heterocycles and can be converted into many other functional groups, such as amines, amides, and ketones. Classical methods for synthesizing nitriles typically involve the dehydration of amides or oximes, as well as Sandmeyer reactions, Rosenmond-von Braun reactions, and transition metal-catalyzed cross-coupling reactions.

[0003] Aldehyde dehydration is a simple method for synthesizing nitriles. Currently, aldehyde dehydration mainly relies on noble metal catalysts or rare earth metal catalysts. Early reports date back to 2001, when Chang's group rapidly dehydrated various aldehyde oximes to nitriles at 80°C using carbon-supported divalent ruthenium species. Later, Hisashi's group used rhenium(VII) oxygen complexes as catalysts to dehydrate aldehyde oximes to the corresponding nitriles, but this reaction system was complex and required high reaction temperatures. In 2005, Prakash and Olah achieved the conversion of aldehyde oximes to nitriles using gallium trifluoromethanesulfonate Ga(OTf)3. Subsequently, Mizuno used a simple co-precipitation method to prepare tungsten-tin mixed hydroxides or ruthenium hydroxide as heterogeneous catalysts to dehydrate various aldehyde oximes to the corresponding nitriles; they later developed alumina-supported rhodium catalysts to achieve the same goal. In 2009, Kim's group also achieved this process using a noble metal palladium catalyst. In 2016, Kang Yanbiao's research group used tin chloride or gallium chloride as catalysts to dehydrate various aldoximes to nitriles under reflux at 80°C. In addition, inexpensive copper or iron-based catalysts can also promote the dehydration of aldoximes to nitriles. In 2013, Lu Ming's research group used copper acetate as a catalyst to convert aldoximes to the corresponding nitriles; in 2016, Uchida's group developed an iron-catalyzed dehydration reaction of aldoximes to nitriles, using ferric trifluoromethanesulfonate as a catalyst to achieve the conversion of aldoxime compounds to nitriles.

[0004] In recent years, chemists have also developed methods for the dehydration of aldoximes to nitrile compounds mediated by small organic molecules. For example, Kokare and Shinde used diethyl phosphate 2-phenylbenzimidazole-1-yl ester as a catalyst to achieve the dehydration of aromatic aldoximes to the corresponding nitrile compounds. The Lakshman group used 1-protected benzotriazole as a dehydrating agent to efficiently convert aldoximes to nitrile compounds in the presence of bases such as DBU. The Mandal group found that sulfonates of oximes can promote the dehydration of aldoximes to nitrile compounds in the presence of DBU. Rezaei developed a method for the dehydration of aldoximes to nitrile compounds catalyzed by sulfuric acid supported on melamine-formaldehyde resin (MFR) under solvent-free conditions. However, the methods reported in the above literature require the aldoximes to be prepared in advance from aldehydes or alcohols, and the reaction conditions are relatively harsh; the use of high temperatures and oxidative conditions limits the substrate range for aldoxime dehydration.

[0005] Compared to aldoximes, the direct synthesis of nitriles from aldehydes reduces synthetic steps and eliminates the need for oxime separation, making it more efficient and economical. Aldehydes are widely available, and large quantities can be purchased commercially. In 2009, Reddy reported the first example of nitrile synthesis from aldehydes using an iodine reagent (KI / I₂-TBHP) as a catalyst. In 2013, Leadbeater reported the synthesis of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxotetrafluoroborate ammonium (4-AcNH-TEMPO-BF₄) and 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxo radical (4-AcNH-TEMPO) and their application to the synthesis of cyanides from aldehydes. The results showed that in the presence of pyridine, hexamethyldisilazane can react with various aromatic or alkyl aldehydes to generate the corresponding nitriles. Subsequently, chemists combined transition metal catalysis, electrocatalysis, photocatalysis and other methods to develop various TEMPO-mediated synthetic routes from aldehydes to nitriles, which effectively promoted the development of nitrile synthesis.

[0006] The development of various nitrogen sources has further enriched the synthetic routes of nitriles. For example, Nantz used diphenylphosphonohydroxylamine as a reagent to realize the conversion of aldehydes to nitriles; Prabhu used acetyloxyoxime acid (AHA) as a nitrogen source and bismuth trifluoromethanesulfonate as a catalyst to convert various aldehydes into corresponding nitriles; Yu's group used 4-trifluoromethyl-benzoyl-hydroxylamine (CF3-BHA) as a nitrogen source to realize the synthesis of aldehydes to nitriles in the presence of protic acids; Hyodo used protected oximes as nitrogen sources and trifluoromethanesulfonate as a catalyst to realize the conversion of aldehydes to nitriles at room temperature; Fokin and Hammond also realized this conversion using sulfuryl fluoride (SO2F2) or HCl·DMPU as catalysts and hydroxylamine hydrochloride as a nitrogen source.

[0007] The development of heterogeneous catalysts has also facilitated the synthetic conversion of aldehydes to nitriles. In 2010, Yamaguchi used alumina-supported ruthenium hydroxide as a reusable heterogeneous catalyst to convert various aldehydes into their corresponding nitriles; in 2012, Jagadeesh reported that carbon nitride-supported iron oxide (Fe2O3-N / C) could catalyze the synthesis of nitriles from aldehydes and ammonia under mild conditions; and in 2019, Rai reported a visible light-driven, highly efficient conversion of aldehydes to nitriles using Co@g-C3N4 as a catalyst.

[0008] However, the methods reported above still face challenges such as high reaction temperatures, complex reaction systems, and high prices of reagents. Therefore, developing a universal and mild synthetic route to synthesize cyanide compounds from aldehydes is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0009] The purpose of this invention is to provide a route for synthesizing organonitrile compounds that is universally applicable, has mild reaction conditions, and is green and economical.

[0010] Therefore, the above-mentioned objective of the present invention is achieved through the following technical solution:

[0011] A method for synthesizing organonitrile compounds from aldehydes includes the following steps:

[0012] Using acetonitrile as a solvent and trifluoroacetic acid as a reaction aid, hydrogen amine hydrochloride reacts with aldehydes at room temperature for a certain time to obtain organic nitrile compounds;

[0013] The reaction route is as follows:

[0014]

[0015] Wherein: R is a substituted or unsubstituted phenyl group, a substituted or unsubstituted five-membered heteroaromatic ring group containing a heteroatom selected from O, S, N, a substituted or unsubstituted C1-12 alkyl group, or a substituted or unsubstituted styryl group.

[0016] The substitution is one or more independent halogens, acetyl groups, trifluoromethyl groups, C1-C4 alkyl groups, or C1-C4 alkoxy groups. The halogen is fluorine, chlorine, bromine, or iodine.

[0017] While adopting the above technical solutions, the present invention may also adopt or combine the following technical solutions:

[0018] As a preferred embodiment of the present invention, the C1-12 alkyl group is a saturated straight-chain or branched hydrocarbon group having 1-12 carbon atoms.

[0019] As a preferred embodiment of the present invention: the C1-4 alkyl refers to a saturated straight-chain or branched hydrocarbon group having 1-4 carbon atoms; for example: methyl, ethyl, n-propyl, isopropyl, tert-butyl, etc.

[0020] As a preferred embodiment of the present invention, the aldehyde compound is: benzaldehyde, 4-methylbenzaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-methoxybenzaldehyde, 4-acetylbenzaldehyde, 3-chloro-4-bromobenzaldehyde, 4-chloro-3-trifluoromethylbenzaldehyde, 3-phenyl-2-propenal, undecylaldehyde, 5-hydroxymethylfurfural, or 5-formyl-2-furanic acid.

[0021] As a preferred embodiment of the present invention, the molar ratio of the hydrogen amine hydrochloride to the aldehyde compound is 1 to 3.

[0022] As a preferred embodiment of the present invention, the molar ratio of the hydrogen amine hydrochloride to the aldehyde compound is preferably 2.5.

[0023] As a preferred embodiment of the present invention, the volume ratio of trifluoroacetic acid to acetonitrile is 0.05 to 0.5.

[0024] As a preferred embodiment of the present invention, the volume ratio of trifluoroacetic acid to acetonitrile is preferably 0.075 to 0.15.

[0025] As a preferred embodiment of the present invention, the room temperature is 20-40℃.

[0026] As a preferred embodiment of the present invention, the reaction time is 12 hours.

[0027] As a preferred embodiment of the present invention, the reaction between hydrogen amine hydrochloride and aldehyde compounds is quenched by a saturated sodium bicarbonate aqueous solution or water.

[0028] This invention provides a method for synthesizing organic nitrile compounds from aldehydes. In the presence of trifluoroacetic acid, the reactants aldehyde and hydroxylamine hydrochloride are reacted directly to prepare organic nitrile compounds in a reactor. This method avoids the traditional technical route for organic nitrile compounds and uses commercially available aldehydes and hydroxylamine hydrochloride as reactants to synthesize nitrile compounds in one step. It is a novel, green, safe, and low-harmful synthetic method for humans and the environment.

[0029] Specifically, compared with the prior art, the present invention has the following beneficial effects:

[0030] 1) The method provided by this invention avoids the use of strong oxidants and transition metal catalysts, does not require high temperature to promote the reaction, is compatible with air, is green and efficient, economical and practical, and clean and environmentally friendly, and has significant advantages in catalytic activity;

[0031] 2) The method provided by this invention uses commercially available hydroxylamine hydrochloride for the reaction, which has good selectivity, simple purification process, high yield, and is applicable to a variety of substituent groups (e.g., halogens, alcohols, ketones, acids, cyano groups, heterocycles, etc.), and is an easy-to-promote synthetic method. Attached Figure Description

[0032] Figure 1 The cyanide-containing compound prepared in Example 1 1 H NMR spectrum.

[0033] Figure 2 The cyanide-containing compound prepared in Example 1 13 C10 NMR spectrum.

[0034] Figure 3 The cyanide-containing compound prepared in Example 2 1 H NMR spectrum.

[0035] Figure 4 The cyanide-containing compound prepared in Example 2 13 C10 NMR spectrum.

[0036] Figure 5 The cyanide-containing compound prepared in Example 3 1 H NMR spectrum.

[0037] Figure 6 The cyanide-containing compound prepared in Example 3 13 C10 NMR spectrum.

[0038] Figure 7 The cyanide-containing compound prepared in Example 3 19 F NMR spectrum.

[0039] Figure 8 The cyanide-containing compound prepared in Example 4 1 H NMR spectrum.

[0040] Figure 9 The cyanide-containing compound prepared in Example 4 13 C10 NMR spectrum.

[0041] Figure 10 The cyanide-containing compound prepared in Example 5 1 H NMR spectrum.

[0042] Figure 11 The cyanide-containing compound prepared in Example 5 13 C10 NMR spectrum.

[0043] Figure 12 The cyanide-containing compound prepared in Example 6 1 H NMR spectrum.

[0044] Figure 13 The cyanide-containing compound prepared in Example 6 13 C10 NMR spectrum.

[0045] Figure 14 The cyanide-containing compound prepared in Example 7 1 H NMR spectrum.

[0046] Figure 15 The cyanide-containing compound prepared in Example 7 13 C10 NMR spectrum.

[0047] Figure 16 The cyanide-containing compound prepared in Example 8 1 H NMR spectrum.

[0048] Figure 17 The cyanide-containing compound prepared in Example 8 13 C10 NMR spectrum.

[0049] Figure 18 The cyanide-containing compound prepared in Example 8 19 F NMR spectrum.

[0050] Figure 19 The cyanide-containing compound prepared in Example 9 1 H NMR spectrum.

[0051] Figure 20 The cyanide-containing compound prepared in Example 9 13 C10 NMR spectrum.

[0052] Figure 21 The cyanide-containing compound prepared in Example 10 1 H NMR spectrum.

[0053] Figure 22 The cyanide-containing compound prepared in Example 10 13 C10 NMR spectrum.

[0054] Figure 23 The cyanide-containing compound prepared in Example 11 1 H NMR spectrum.

[0055] Figure 24 The cyanide-containing compound prepared in Example 11 13 C10 NMR spectrum.

[0056] Figure 25 The cyanide-containing compound prepared in Example 12 1 H NMR spectrum.

[0057] Figure 26 The cyanide-containing compound prepared in Example 13 13 C10 NMR spectrum. Detailed Implementation

[0058] It should be noted that for experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0059] This invention provides a method for synthesizing nitrile compounds, mainly as follows:

[0060] Hydroxylamine hydrochloride reacts with aldehydes at room temperature to give cyanide-containing compounds. The catalyst is trifluoroacetic acid, the solvent is acetonitrile, and the yield is 87%-96%.

[0061] According to the above synthetic method, the following compounds were synthesized. In this invention, different substituents have little effect on the reactivity of the compounds:

[0062]

[0063] Specifically, the present invention will be further described in detail through the following specific experimental embodiments.

[0064] Example 1

[0065] This embodiment provides the preparation of benzonitrile, and the reaction route is shown below:

[0066]

[0067] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.53 mL of benzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was allowed to proceed at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to obtain 490 mg of a clear oily liquid, with a yield of 95%.

[0068] The benzonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 1-2 The data results are shown below:

[0069] 1 HNMR (400MHz, CDCl3) δ7.63-7.54 (m, 3H), 7.43 (dd, J = 8.4, 7.1Hz, 2H).

[0070] 13 C NMR (101MHz, CDCl3) δ132.84,132.12,129.17,118.87,112.36.

[0071] Example 2

[0072] This embodiment provides the preparation of 4-methylbenzonitrile, and the reaction route is shown below:

[0073]

[0074] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.39 mL of 4-methylbenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was allowed to proceed at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to obtain 520.9 mg of a white solid, with a yield of 89%.

[0075] The p-4-methylbenzonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 3-4 The data results are shown below:

[0076] 1 HNMR (400MHz, CDCl3) δ7.53 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 2.42 (s, 3H).

[0077] 13 C NMR (101MHz, CDCl3) δ143.75,132.04,129.87,119.19,109.28,21.85.

[0078] Example 3

[0079] This embodiment provides the preparation of 5-hydroxymethyl-2-furanonitrile, and the reaction route is shown below:

[0080]

[0081] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.621 mL of 4-fluorobenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to give 568.7 mg of a white solid, with a yield of 94%.

[0082] The 4-fluorobenzonitrile prepared in this example was subjected to 1H NMR, 1C NMR, and fluorine NMR spectroscopy. Detailed spectra are shown in [reference needed]. Figures 5-7 The data results are shown below:

[0083] 1 HNMR (400MHz, CDCl3) δ7.73-7.62 (m, 2H), 7.17 (t, J = 8.6Hz, 2H).

[0084] 13 C NMR (101MHz, CDCl3) δ166.33,163.78,134.76,134.67,118.06,117.00,116.78,108.60,108.56.

[0085] 19 F NMR (376MHz, CDCl3) δ -102.39.

[0086] Example 4

[0087] This embodiment provides the preparation of 4-chlorobenzonitrile, and the reaction route is shown below:

[0088]

[0089] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.729 g of 4-chlorobenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to give 685 mg of white solid, with a yield of 87%.

[0090] The p-4-chlorobenzonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 8-9 The data results are shown below:

[0091] 1 HNM (400MHz, CDCl3) δ7.60 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H).

[0092] 13 C NMR (101MHz, CDCl3) δ139.57,133.41,129.72,117.99,110.79.

[0093] Example 5

[0094] This embodiment provides the preparation of 4-methoxybenzonitrile, and the reaction route is shown below:

[0095]

[0096] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.61 mL of 4-methoxybenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and dichloromethane, volume ratio 5:2) to obtain 596 mg of white solid, with a yield of 90%.

[0097] The p-4-methylbenzonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 10-11 The data results are shown below:

[0098] 1 HNMR (400MHz, CDCl3) δ7.59 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H).

[0099] 13 C NMR (101MHz, CDCl3) δ162.85,134.01,119.27,114.76,103.97,55.57

[0100] Example 6

[0101] This embodiment provides the preparation of 4-acetylbenzonitrile, and the reaction route is shown below:

[0102]

[0103] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.74 g of 4-acetylbenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to give 631 mg of white solid, with a yield of 87%.

[0104] The p-4-acetylbenzonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 12-13 The data results are shown below:

[0105] 1 H NMR (400MHz, CDCl3) δ8.04(d,J=8.5Hz,2H),7.77(d,J=8.6Hz,2H),2.64(s,3H).

[0106] 13 C NMR (101MHz, CDCl3) δ196.55,139.93,132.54,128.72,117.94,116.43,26.79.

[0107] Example 7

[0108] This embodiment provides the preparation of 3-chloro-4-bromobenzonitrile, and the reaction route is shown below:

[0109]

[0110] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 1.02 g of 3-chloro-4-bromobenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was allowed to proceed at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and dichloromethane, volume ratio 5:1) to give 1.06 g of a white solid, with a yield of 88%.

[0111] The p-3-chloro-4-bromobenzonitrile prepared in this example was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 14-15 The data results are shown below:

[0112] 1 HNMR (400MHz, CDCl3) δ7.78-7.73 (m, 2H), 7.41 (dd, J = 8.3, 1.9Hz, 1H).

[0113] 13 C NMR (101MHz, CDCl3) δ136.01,134.76,133.40,130.94,128.63,116.90,112.67.

[0114] Example 8

[0115] This embodiment provides the preparation of 4-chloro-3-trifluoromethylbenzonitrile, and the reaction route is shown below:

[0116]

[0117] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 1.04 g of 4-chloro-3-trifluoromethylbenzaldehyde (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and dichloromethane, volume ratio 5:1) to obtain 932 mg of white solid, with a yield of 88%.

[0118] The p-3-chloro-4-bromobenzonitrile prepared in this example was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 16-18 The data results are shown below:

[0119] 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 1.9 Hz, 1H), 7.78 (dd, J = 8.4, 2.0 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H).

[0120] 13 C NMR (101MHz, CDCl3) δ136.74,135.01,131.70,130.32,130.27,130.22,130.16,129.22,128.90,122.03,119.31,115.65,110.44.

[0121] 19 F NMR (376MHz, CDCl3) δ -63.32.

[0122] Example 9

[0123] This embodiment provides the preparation of 3-phenyl-2-propenyl carbide, and the reaction route is shown below:

[0124]

[0125] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 40 mL of acetonitrile (MeCN) to dissolve it. 0.66 g of 3-phenyl-2-propenal (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 35 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and ethyl acetate, volume ratio 10:1). After rotary evaporation, 620 mg of a clear oily liquid was obtained, with a yield of 96%.

[0126] The p-3-phenyl-2-acrylonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See attached images for detailed spectra. Figures 19-20 The data results are shown below:

[0127] 1 HNMR (400MHz, CDCl3) δ7.50-7.37 (m, 6H), 5.88 (d, J = 16.7Hz, 1H).

[0128] 13 C NMR (101MHz, CDCl3) δ150.62,133.54,131.26,129.15,127.40,118.21,96.36.

[0129] Example 10

[0130] This embodiment provides the preparation of undecanoic acid nitrile, and the reaction route is shown below:

[0131]

[0132] 1.737 g of hydroxylamine hydrochloride (NH₂OH·HCl, 25 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 40 mL of acetonitrile (MeCN) to dissolve it. 1.70 g of undecylaldehyde (10 mmol) was added, followed by 6 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with 70 mL of saturated NaHCO₃ aqueous solution until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed once with saturated brine, dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: n-hexane), and after rotary evaporation, 1.57 g of a colorless oily liquid was obtained, with a yield of 95%.

[0133] The undecanocyanine prepared in this embodiment was subjected to 1H and 1C NMR spectra. See attached images for detailed spectra. Figures 21-22 The data results are shown below:

[0134] 1 H NMR (400MHz, CDCl3) δ2.33 (t, J = 7.1Hz, 2H), 1.65 (p, J = 7.2Hz, 2H), 1.44 (t, J = 7.5Hz, 2H), 1.27 (d, J = 8.4Hz, 12H), 0.88 (t, J = 6.7Hz, 3H).

[0135] 13 C NMR (101MHz, CDCl3) δ119.89,31.86,29.47,29.32,29.26,28.77,28.68,25.39,22.67,17.14,14.11.

[0136] Example 11

[0137] This embodiment provides the preparation of 5-hydroxymethyl-2-furanonitrile, and the reaction route is shown below:

[0138]

[0139] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.63 g of 5-hydroxymethylfurfural (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction mixture was reacted at room temperature for 12 h. After the reaction was complete, the mixture was quenched with water, and the liquid reaction mixture was transferred to a separatory funnel. The aqueous phase was extracted three times with dichloromethane, and the combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and tetrahydrofuran, volume ratio 4:1) to give 590.4 mg of white solid, with a yield of 96%.

[0140] The p-5-hydroxymethyl-2-furanonitrile prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 23-24 The data results are shown below:

[0141] 1 HNMR (400MHz, CDCl3) δ7.06 (d, J = 3.6 Hz, 1H), 6.50 (d, J = 3.6 Hz, 1H), 4.56 (s, 2H).

[0142] 13C NMR (101MHz, CDCl3) δ155.31,126.55,122.91,111.04,110.76,36.06.

[0143] Example 12

[0144] This embodiment provides the preparation of 5-cyano-2-furanic acid, and the reaction route is shown below:

[0145]

[0146] 0.868 g of hydroxylamine hydrochloride (NH₂OH·HCl, 12.5 mmol) was weighed and added to a 100 mL round-bottom flask, followed by 20 mL of acetonitrile (MeCN) to dissolve it. 0.70 g of 5-formyl-2-furanic acid (5 mmol) was added, followed by 3 mL of trifluoroacetic acid. The reaction was carried out at room temperature for 12 h. After the reaction was complete, the mixture was quenched with water, and the liquid reaction mixture was transferred to a separatory funnel. The aqueous phase was extracted three times with dichloromethane, and the combined organic phases were washed once with saturated brine. The mixture was dried over anhydrous magnesium sulfate for 30 minutes, filtered through diatomaceous earth, and the resulting solution was concentrated by rotary evaporation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether and ethyl acetate, volume ratio 1:1, with the addition of 1% acetic acid) to obtain 637 mg of white solid, with a yield of 93%.

[0147] The p-5-cyano-2-furanic acid prepared in this embodiment was subjected to 1H and 1C NMR spectra. See the detailed spectra below. Figures 25-26 The data results are shown below:

[0148] 1 HNMR (400MHz, DMSO) δ7.72 (d, J = 3.8, 1H), 7.40 (d, J = 3.8, 1H).

[0149] 13 C NMR (101MHz, DMSO) δ158.48,149.38,127.38,125.11,118.34,111.50.

[0150] The above specific embodiments are used to explain and illustrate the present invention, and are only preferred embodiments of the present invention, not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made to the present invention within the spirit and scope of the claims shall fall within the protection scope of the present invention.

Claims

1. A method for synthesizing organonitrile compounds from aldehydes, characterized in that: The method includes the following steps: Using acetonitrile as a solvent and trifluoroacetic acid as a reaction aid, hydroxylamine hydrochloride reacts with aldehydes at room temperature for a certain time to obtain organic nitrile compounds; The reaction route is as follows: Wherein: R is a substituted or unsubstituted phenyl group, a substituted or unsubstituted five-membered heteroaromatic ring group containing a heteroatom selected from O, S, N, a substituted or unsubstituted C1-12 alkyl group, or a substituted or unsubstituted styryl group. The substitution is one or more independent halogens, acetyl groups, trifluoromethyl groups, C1-C4 alkyl groups, or C1-C4 alkoxy groups.

2. The method according to claim 1, characterized in that: The C1-12 alkyl group is a saturated straight-chain or branched hydrocarbon group having 1-12 carbon atoms.

3. The method according to claim 1, characterized in that: The C1-4 alkyl group refers to a saturated straight-chain or branched hydrocarbon group having 1-4 carbon atoms.

4. The method according to claim 1, characterized in that: The aldehyde compounds are: benzaldehyde, 4-methylbenzaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-methoxybenzaldehyde, 4-acetylbenzaldehyde, 3-chloro-4-bromobenzaldehyde, 4-chloro-3-trifluoromethylbenzaldehyde, 3-phenyl-2-propenal, or undecanoal.

5. The method according to claim 1 or 4, characterized in that: The molar ratio of hydroxylamine hydrochloride to aldehyde compounds is 1 to 3.

6. The method according to claim 5, characterized in that: The molar ratio of hydroxylamine hydrochloride to aldehyde compounds is 2.

5.

7. The method according to claim 1, characterized in that: The volume ratio of trifluoroacetic acid to acetonitrile is 0.05~0.

5.

8. The method according to claim 7, characterized in that: The volume ratio of trifluoroacetic acid to acetonitrile is 0.075~0.

15.

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

10. The method according to claim 1, characterized in that: The reaction between hydroxylamine hydrochloride and aldehydes is quenched with a saturated aqueous solution of sodium bicarbonate or water.

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