CN109776298B - Synthetic method of cinnamaldehyde compound - Google Patents

Abstract

The invention discloses a method for synthesizing cinnamaldehyde compounds, which takes aliphatic aldehyde and substituted aromatic hydrocarbon as initial raw materials, takes palladium compound and amino acid as catalysts, and synthesizes the cinnamaldehyde compounds through cross dehydrogenation coupling reaction. Compared with the traditional synthesis method of the cinnamaldehyde compounds, the method has the advantages of simple operation, mild reaction conditions, low price of used reagents, high efficiency and high atom utilization rate.

Description

Synthetic method of cinnamaldehyde compound

Technical Field

The invention relates to a novel method for synthesizing cinnamaldehyde compounds, and belongs to the field of organic synthesis.

Background

Cinnamaldehyde is a very valuable organic compound which is widely used as a flavoring agent in chewing gums, ice creams, confections and beverages, as an antiviral and anticancer agent, or as an effective fungicide, agrochemical insecticide, and as a corrosion inhibitor for steel or other iron alloys in corrosive fluids such as hydrochloric acid. In addition, cinnamaldehyde is an important multifunctional intermediate in organic synthesis. The traditional synthesis methods of cinnamaldehyde compounds mainly comprise two methods, wherein one method is obtained by cross-coupling reaction of olefine aldehyde and aryl halide or aryl boric acid compounds; the other is prepared by a benzaldehyde compound and a catalyst containingα-hydrogen is produced by aldol condensation under basic conditions. The first method requires pre-functionalization of the raw materials to prepare the corresponding reaction precursor (such as aryl halide or aryl boronic acid compound), and the steps are complicated, and in addition, some aryl boronic acid compounds have high activity and harsh reaction conditions. The second method requires weakly basic conditions for preparing cinnamaldehyde, and is unstable in a strongly acidic or strongly basic medium, so that the reaction substrate is greatly limited. Thus, these conventional methods are advantageous in terms of step simplicity, operability, and atom economyThere is a large lifting space.

The formation of C-C bonds is the basic transformation subject of organic chemistry forever. Transition metal-catalyzed cross-coupling reactions have become a very valuable tool in organic chemistry for over 40 years to build C-C bonds. The transition metal catalyzed direct oxidative dehydrogenation cross-coupling reaction is an important branch of the reaction, and is to form a new C-C bond by breaking two C-H bonds. Such reactions avoid the need for pre-functionalization of the starting materials, making the synthetic schemes shorter and more efficient, while reducing costs and waste, and are considered to be the most desirable chemical reaction.

Disclosure of Invention

The invention aims to provide a method for synthesizing cinnamaldehyde compounds, which has the advantages of simple operation, low cost, high efficiency and high atom utilization rate and meets the requirement of green chemistry.

The invention is realized as follows:

a method for synthesizing cinnamaldehyde compounds comprises the following steps: taking the compound A and the compound B as initial raw materials, taking a palladite and amino acid as catalysts, preparing the cinnamaldehyde compound C,

in the formula, R¹Is methyl or hydrogen;

R²and R³Independently selected from alkyl of H, C1-C6, alkoxy of C1-C6 or halogen group, wherein R is²And R³Not H at the same time or not;

or the compound B is

Or

。

The amino acid is alpha-amino acid orβ-amino acids, preferablyβ-alanine.

The palladium compound is palladium acetate, palladium trifluoroacetate or palladium chloride.

An oxidant is added in the reaction process, and the oxidant is potassium peroxodisulfate or oxygen.

An additive is also added in the reaction process, and the additive is trifluoroacetic acid.

Compared with the traditional synthetic method of the cinnamaldehyde compound, the method has the advantages of simple operation, saving, high efficiency and high atom utilization rate.

Detailed description of the invention

The synthesis method comprises the following steps: a palladium catalyst (10 mol%), amino acid (50 mol%), oxidant, aromatic hydrocarbon and aliphatic aldehyde are sequentially added into a sealed tube, and then a solvent and an additive are added. The reaction tube was then sealed and stirred at room temperature for 10 minutes, followed by stirring in an oil bath at 60 ℃ for 24 hours. The reaction was checked by TLC plate until the starting material reaction was complete. After the reaction was complete the reaction tube was cooled to room temperature, the reaction mixture was filtered through celite (ethyl acetate wash) and the filtrate was concentrated in vacuo. Finally, the cinnamaldehyde compound is obtained by column chromatography separation and purification.

Example 1

Palladium acetate (4.5 mg, 10 mol%) was charged in this order in a 15mL sealed tube,βalanine (8.9 mg, 0.1 mmol, 50 mol%), potassium peroxodisulfate (108.1 mg, 0.4 mmol, 2 equiv), anisole (0.11 mL, 1.0 mmol, 5 equiv) and 2-methylpropanal (18.3)μL, 0.2mmol, 1 equiv), followed by 1mL acetonitrile, and finally trifluoroacetic acid (0.139 mL, 1.8 mmol, 9 equiv) with stirring. The reaction tube was then sealed, stirred at room temperature for 10 minutes and subsequently placed at a temperature of 60 deg.C^oC stirring in oil bath for 24 hours. After the reaction was complete the reaction tube was cooled to room temperature, the reaction mixture was filtered through celite (ethyl acetate wash) and the filtrate was concentrated in vacuo. Finally, separation and purification by column chromatography gave compound C-1 (24.3 mg,69%）。

compound C-1: a yellow oil; IR (KBr) 2927, 2841, 1674, 1601, 1510, 1257, 1180, 1016, 827, 536 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 9.54 (s, 1H), 7.53 (d, J= 8.8 Hz, 2H), 7.19 (s, 1H), 6.98 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.08 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 195.6, 160.9, 149.9, 136.4, 132.2, 128.2, 114.4, 55.5, 11.1; HRMS (ESI) m/z calculated for C₁₁H₁₃O₂ [M+H]⁺: 177.0910; found: 177.0905。

Example 2

Palladium acetate (4.5 mg, 10 mol%) was charged in this order in a 15mL sealed tube,βalanine (8.9 mg, 0.1 mmol, 50 mol%), potassium peroxodisulfate (108.1 mg, 0.4 mmol, 2 equiv), cumene (1 mL) and 2-methylpropanal (18.3)μL, 0.2mmol, 1 equiv), and finally trifluoroacetic acid (0.139 mL, 1.8 mmol, 9 equiv) was added with stirring. The reaction tube was then sealed, stirred at room temperature for 10 minutes and subsequently placed at a temperature of 60 deg.C^oC stirring in oil bath for 24 hours. After the reaction was complete the reaction tube was cooled to room temperature, the reaction mixture was filtered through celite (ethyl acetate wash) and the filtrate was concentrated in vacuo. Final purification by column chromatography gave Compound C-2 (21.4 mg, 57%).

Compound C-2: a yellow oil; IR (KBr) 2962, 2925, 2870, 2711, 1680, 1626, 1458, 1360, 1311, 1188, 1014, 892, 822, 555 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 9.57 (s, 1H), 7.49 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.25 (s, 1H), 2.96 (hept, J = 7.0 Hz, 1H), 2.09 (s, 3H), 1.28 (d, J = 6.9 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 195.8, 151.1, 150.2, 137.7, 132.9, 130.5, 127.0, 34.2, 23.9, 11.1; HRMS (ESI) m/z calculated for C₁₃H₁₆NaO [M+Na]⁺: 211.1093; found: 211.1090。

Example 3

Palladium acetate (4.5 mg, 10 mol%) was charged in this order in a 15mL sealed tube,βalanine (8.9 mg, 0.1 mmol, 50 mol%), potassium peroxodisulfate (108.1 mg, 0.4 mmol, 2 equiv), 4-tert-butyl methyl ether (0.18 mL, 1.0 mmol, 5 equiv) and 2-methylpropanal (18.3)μL, 0.2mmol, 1 equiv), followed by 1mL acetonitrile, and finally trifluoroacetic acid (0.139 mL, 1.8 mmol, 9 equiv) with stirring. The reaction tube was then sealed, stirred at room temperature for 10 minutes and subsequently placed at a temperature of 60 deg.C^oC stirring in oil bath for 24 hours. After the reaction was complete the reaction tube was cooled to room temperature, the reaction mixture was filtered through celite (ethyl acetate wash) and the filtrate was concentrated in vacuo. Final purification by column chromatography gave Compound C-3 (24.6 mg, 53%).

Compound C-3: a yellow oil; IR (KBr) 2958, 2867, 2709, 1684, 1622, 1496, 1444, 1257, 1194, 1022, 818 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 9.63 (s, 1H), 7.62 (s, 1H), 7.48 (d, J = 2.5 Hz, 1H), 7.40 (dd, J = 8.7, 2.6 Hz, 1H), 6.89 (d, J= 8.6 Hz, 1H), 3.87 (s, 3H), 2.04 (s, 3H), 1.33 (s, 9H); ¹³C NMR (100 MHz, CDCl₃) δ 196.1, 155.6, 145.8, 143.1, 138.2, 128.0, 127.4, 123.5, 110.5, 55.8, 34.3, 31.6, 11.2; HRMS (ESI) m/z calculated for C₁₅H₂₁O₂ [M+H]⁺: 233.1536; found: 233.1537。

Example 4

Palladium acetate (4.5 mg, 10 mol%) was charged in this order in a 15mL sealed tube,β-alanine(8.9 mg, 0.1 mmol, 50 mol%), potassium peroxodisulfate (108.1 mg, 0.4 mmol, 2 equiv), 2, 3-dihydrobenzofuran (0.11 mL, 1.0 mmol, 5 equiv) and n-propionaldehyde (14.4μL, 0.2mmol, 1 equiv), followed by 1mL acetonitrile, and finally trifluoroacetic acid (0.139 mL, 1.8 mmol, 9 equiv) with stirring. The reaction tube was then sealed, stirred at room temperature for 10 minutes and subsequently placed at a temperature of 60 deg.C^oC stirring in oil bath for 24 hours. After the reaction was complete the reaction tube was cooled to room temperature, the reaction mixture was filtered through celite (ethyl acetate wash) and the filtrate was concentrated in vacuo. Finally separating and purifying by column chromatography to obtain compound C⁴（18.5mg，53%）。

Compound C-4: white solid, melting point 65-66^oC；IR (KBr): 2923, 2854, 2798, 1664, 1600, 1491, 1240, 1124, 976, 808, 613 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 9.63 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H), 7.40 (d, J = 15.8 Hz, 1H), 7.34 (dd, J = 8.2, 1.9 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 6.58 (dd, J = 15.8, 7.7 Hz, 1H), 4.65 (t, J = 8.7 Hz, 2H), 3.25 (t, J = 8.7 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 193.9, 163.4, 153.4, 130.6, 128.6, 127.1, 126.1, 125.0, 110.1, 72.2, 29.3; HRMS (ESI) m/z calculated for C₁₁H₁₁O₂ [M+H]⁺: 175.0754; found: 175.0759。

Claims (3)

1. A method for synthesizing cinnamaldehyde compounds is characterized in that: taking a compound A and a compound B as initial raw materials, taking a palladium compound and amino acid as catalysts, preparing a cinnamaldehyde compound C, wherein the palladium compound is palladium acetate, palladium trifluoroacetate or palladium chloride, an oxidant and an additive are also added in the reaction, the oxidant is potassium peroxodisulfate or oxygen, the additive is trifluoroacetic acid,

in the formula, R¹Is methyl or hydrogen;

R²and R³Independently selected from alkyl of H, C1-C6, alkoxy of C1-C6 or halogen group, wherein R is²And R³Not H at the same time or not;

or the compound B is

Or

。

2. The method for synthesizing cinnamaldehyde compounds according to claim 1, wherein: the amino acid is alpha-amino acid orβ-an amino acid.

3. The method for synthesizing cinnamaldehyde compounds according to claim 2, wherein: the amino acid isβ-alanine.