CN107176899A - The method that a kind of dioxygen oxidation alcohol or aldehyde prepare acid - Google Patents

Abstract

The invention provides a method for preparing acid by oxidizing alcohol or aldehyde with oxygen or oxygen in the air as an oxidant. It is at room temperature in an organic solvent with iron nitrate (Fe(NO ₃ ) ₃ .9H ₂ O), 2 , 2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO) and inorganic halides are used as catalysts, oxygen or air is used as oxidant, and alcohol or aldehyde is oxidized to generate acid, and diol is oxidized to generate lactone; or, with Aldehydes are used as raw materials, and ferric nitrate is used as a catalyst to react under neutral conditions, and the aldehydes are oxidized to generate acid and peroxyacid. The invention has the advantages of environmental protection, low cost, high yield, high atom economy, good substrate functional group compatibility, mild reaction conditions, scalable reaction scale, etc., and is suitable for industrial production.

Description

A kind of method that oxygen oxidation alcohol or aldehyde prepares acid

technical field

The invention relates to a method for producing acid by oxidizing alcohol or aldehyde by using oxygen or oxygen in air as an oxidant, in particular to a method for producing acid by oxidizing alcohol or aldehyde with iron catalysis.

Background technique

Carboxylic acid is an important class of organic compounds, widely used in industry, agriculture, medicine and people's daily life. The oxidation reaction from alcohol to acid is a fundamental and important chemical reaction in organic chemistry. In industry and pharmaceuticals, carboxylic acids are often produced by oxidation. Therefore, finding a catalytic oxidation system with high efficiency, low price, mild conditions, good functional group compatibility and environmental friendliness has a good application prospect. The difficulty in converting alcohols to acids is the oxidation of aldehydes to acids. Traditionally, the synthesis of acids is obtained by oxidizing the corresponding alcohols with equivalent or excess oxidizing agents, such as KMnO4 oxidation, Jones' oxidation, and other _{CrO3 -} based oxidation methods, etc. The disadvantage of this type of method is that the oxidant contains heavy metals, is expensive, and the waste liquid pollutes the environment. The reaction often requires strong acidity, harsh conditions, and high equipment requirements. It is not suitable for large-scale industrial production (Oxidation of Primary Alcohols to Carboxylic Acids, Springer: Berlin, 2007; Mahmood, A.; Robinson, GE; Powell, L. Org. Process Res. Dev. 1999, 3, 363-364; Thottathil, JK; Moniot, JL; Mueller, RH; Wong, MKY; Chem. 1986, 51, 3140-3143). Oxygen is a cheap, easy-to-obtain, clean, high-atom-economical, and environmentally friendly oxidizing agent. Air is a more ideal oxidant, without preparation and transportation, and is safer in industrial production. At present, the oxidation methods from alcohol to acid using oxygen as oxidant are very limited, and they are concentrated in the field of noble metal catalysis, and the reports on air oxidation are even rarer. For example, the Pt-catalyzed Heyns oxidation developed in the 1940s, however, the high price and easy poisoning of Pt limit the application of Heyns oxidation in industrial production; Jiang Biao's group realized the use of Ag(NHC)/KOH system in 2014 Dry air oxidizes benzyl alcohol to generate acid; Davis et al. reported that Au/H ₂ O interface catalyzed ethanol and glycerol to generate acid; Zhang Zehui et al. reported that supported magnetic Pd nanocatalyst catalyzed oxygen oxidation of 5-hydroxymethylfurfural 2,5-furandicarboxylic acid; Buffin et al. reported that under the catalysis of Pd, alcohols can be oxidized by oxygen to a mixture of carboxylic acids and esters, and alcohol can be oxidized to a mixture of aldehydes and acids; in 2015, Li Chaojun’s group reported that in In the AgO ₂ /IPr system, acid was generated by oxygen oxidation of aldehyde. Ag, Au, Ru, Pd and other metal-catalyzed oxidation reactions have also been reported, but the substrates have strong limitations, and most of them require nanotechnology or support to realize (Dalmer, O.; Heyns, KUS Pat. 1940, 2, 190, 377; Han, L.; Xing, P.; Jiang, B. Org. Lett. 2014, 16, 3428-3431; Zope, BN; Hibbitts, DD; Neurorock, M.; Davis, RJ Science, 2010, 330, 74-78; Kerdi, F. ; Rass, HA; Pinel, C.; Besson, M.; Peru, G.; Leger, B.; ; Buffin, BP; Clarkson, JP; Belitz, NL; Kundu, AJ Mol. Catal. A. 2005, 225, 111-116; eLiu, MX; ). TEMPO can provide a stable oxygen radical, which plays an important role in the process of synergistically catalyzing the oxidation of alcohols with Fe or Cu to obtain aldehydes or ketones (StahlS.S.; Ryland, BLAngew.Chem.Int.Ed.2014, 53, 8824-8838; Cao, Q.; Dornan, LM; Rogan, L.; Hughes, NL; Muldoon, MJ Chem. Commun., 2014, 50, 4524-4543). However, there have been no reports on the oxidation of alcohols or aldehydes to acids by oxygen in such systems.

Contents of the invention

The invention overcomes the defects in the prior art of using equivalent heavy metals as oxidants or noble metals as catalysts, harsh reaction conditions, poor compatibility of substrate functional groups, high temperature and high pressure required for the reaction, and provides a method that is produced by oxygen or air at room temperature and normal pressure. The method of oxidizing alcohols or aldehydes to generate acids, using ferric nitrate, TEMPO, and inorganic halides that are readily available in the industry as co-catalysts, and using oxygen or air from a wide range of sources as oxidants, reduces costs and reduces waste pollution generated during the reaction process , which has the advantages of high efficiency, mildness, and easy scale-up of the reaction scale.

The purpose of the present invention is to provide a method for preparing acid by catalyzing oxygen oxidation of alcohol or aldehyde with mild reaction conditions, high efficiency, low cost, and environmental protection.

A method for preparing acid by oxygen oxygen oxidation of alcohol or aldehyde provided by the invention, at room temperature, in an organic solvent, with oxygen or oxygen in the air as an oxidant, with alcohol, glycol or aldehyde as raw material, iron nitrate, 2 , 2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO), inorganic halides are used as catalysts, the reaction time is 1-48 hours under neutral conditions, alcohol or aldehyde is oxidized to generate acid, diol is oxidized to generate internal ester or diacid.

In the method of the present invention, the molar ratio of the alcohol, diol or aldehyde, ferric nitrate, 2,2,6,6-tetramethylpiperidine nitrogen oxide, and inorganic halide is 100:1～10:1～20 : 1～10; Preferably, the mol ratio of described alcohol (or aldehyde), ferric nitrate, 2,2,6,6-tetramethylpiperidine nitrogen oxide, inorganic halide is 100:10:20:10 .

The present invention also provides a method for preparing acid by oxidizing alcohol or aldehyde with oxygen. At room temperature, in an organic solvent, oxygen or oxygen in the air is used as an oxidant, aldehyde is used as a raw material, and iron nitrate is used as a catalyst. Under these conditions, the aldehyde is oxidized to form acid and peroxyacid. In the method of the present invention, the molar ratio of the raw material aldehyde to iron nitrate is 100-10:1 to generate corresponding acid and peroxyacid.

In the method of the present invention, the alcohol is R ₁ CH ₂ OH.

Among them, R1 refers to a _C1 -C16 carbon chain, a C3-C8 carbocyclic or heterocyclic ring, an alkyl group containing functional groups such as halogen, aryl group, heterocyclic ring, ester group, ether bond, alkynyl group, double bond, etc., terpene Classes, steroids and other structures;

The halogen is fluorine, chlorine, bromine, iodine;

The aryl is phenyl, alkoxyphenyl, nitrophenyl, halophenyl, furyl or naphthyl; wherein, the alkoxyphenyl is methoxyphenyl, ethoxyphenyl Base, the halogenated phenyl is fluorophenyl, chlorophenyl, bromophenyl, iodophenyl;

The heterocycles are furan rings and thiophene rings.

Preferably, the R is _a C2-C16 carbon chain, a C3-C8 carbocycle or heterocycle, an alkyl group containing functional groups such as halogen, phenyl, heterocycle, ester group, ether bond, alkynyl, double bond, etc. , Terpenes, steroids and other structures.

Further, R ₁ is a carbon chain of C2-C16, a carbon ring of C3-C8, sulfur-containing, oxygen aliphatic heterocyclic ring, containing halogen, phenyl, thienyl, furyl, ester group, ether bond, alkynyl, bis Alkyl groups with functional groups such as bonds, structures such as terpenoids and steroids.

Further, the raw material alcohol is octanol, dodecanol, phenylpropanol, cetyl alcohol, methyl 6-hydroxyhexanoate, 8-acetoxy octanol, tetrahydrofuran-2-methanol, thiophene- 2-Ethanol, 9-bromo-1-nonanol, 2-hexyloxyethanol, 7-alkyne-1-octanol, 4-pentyn-1-ol, 10-undecyn-1-ol, 3- Trimethylsilylpropynol, Cyclohex-3-ene-1-methanol, Octanediol, Sclarediol, (3α,5β)-3,24-Cholediol, Ortho-Phenylenediol.

In the method of the present invention, the aldehyde is R ₂ CHO.

Wherein, the R2 refers to a C1 _- C16 carbon chain, a C3-C8 carbocycle or heterocycle, an alkyl group containing functional groups such as halogen, aryl, heterocycle, ester group, ether bond, alkynyl, double bond, etc. , terpenes, steroids and other structures;

Wherein, the halogen is fluorine, chlorine, bromine, iodine;

The aryl is phenyl, alkoxyphenyl, nitrophenyl, halophenyl, thienyl, furyl or naphthyl, wherein the alkoxyphenyl is methoxyphenyl, ethyl Oxyphenyl, the halogenated phenyl is fluorophenyl, chlorophenyl, bromophenyl, iodophenyl;

The heterocycles are furan rings and thiophene rings.

Preferably, the R2 is a C2 _- C16 carbon chain, a C3-C8 carbocycle or heterocycle, an alkyl group containing functional groups such as halogen, phenyl, heterocycle, ester group, ether bond, alkynyl, double bond, etc. , Terpenes, steroids and other structures.

Further, the R2 is a carbon chain of C2 _- C16, a carbon ring of C3-C8, sulfur-containing, oxygen aliphatic heterocyclic ring, containing halogen, phenyl, thienyl, furyl, ester group, ether bond, alkynyl Alkyl groups with functional groups such as double bonds, terpenes, steroids and other structures.

Further, the raw material aldehydes are octanal, dodecanal, cyclohexyl formaldehyde, and phenylpropionaldehyde.

In the method of the present invention, the diol includes 1,4-diol, 1,5-diol and 1,8-diol.

In the method of the present invention, the organic solvent is ethyl acetate, dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane, 1,2-dichloropropane, 1,3-dichloro One or more mixtures of propane, nitromethane, ethylene glycol dimethyl ether, dioxane, tetrahydrofuran, acetonitrile, benzene or toluene; preferably, the organic solvent is 1,2-dichloroethane .

In the method of the present invention, the inorganic halides are lithium halides, sodium halides, potassium halides, rubidium halides, and cesium halides, and the halogen atoms are fluorine, chlorine, bromine, and iodine. Potassium chloride and sodium chloride are preferred. Potassium chloride is more preferred.

In the method of the present invention, when oxygen is the oxidant, the reaction time is preferably 12 hours; when oxygen in the air is the oxidant, the reaction time is preferably 16 hours.

In the method of the present invention, ferric nitrate is a Lewis acid, and the neutral condition refers to the participation of no protic acid or base, that is, no addition of protonic acid or base.

Further, in the present invention, when the oxygen in the air is used as the oxidant to amplify the reaction, two technical means can also be used to solve the problem of amplifying the reaction in industrial production: one method is to use the air bag as the main source of oxygen, and the reaction is 1.5 Hours later, add oxygen balloons as a supplement; another method is to make the air slowly flow through the reaction vessel through the slow air flow method to achieve the purpose of oxidation. These technical means avoid the dangers that may be brought by the reaction under the condition of pure oxygen in industry, meet the equipment requirements, and are convenient for industrial application.

The reaction mechanism of the present invention is: Int 1, the combined product of TEMPO and Fe ³⁺ , reacts with alcohol to generate Int 2 . Int 2 obtained aldehyde, TEMPOH, Fe ²⁺ by β-elimination and reductive elimination. In the reaction system, Fe ²⁺ can be re-oxidized to Fe ³⁺ under the action of NO ₂ , while NO ² is reduced to NO. _NO2 is regenerated by the reaction of NO with ^O2 . TEMPOH is converted back to TEMPO by reaction with Fe ³⁺ . Aldehyde hydrate Int 3 is generated by H ₂ O attacking aldehyde under the regulation of Fe ³⁺ . The aldehyde hydrate Int 3 undergoes a similar process to give the carboxylic acid, as shown in Figure 1.

The invention discloses that at room temperature, in an organic solvent, Fe(NO ₃ ) ₃ .9H ₂ O, TEMPO (2,2,6,6-tetramethylpiperidine nitrogen oxide), and an inorganic halide ( Such as KCl) as a catalyst, using oxygen or air as an oxidant to oxidize alcohols or aldehydes to generate corresponding acids. The invention also discloses a method for reacting under neutral conditions in an organic solvent with oxygen as an oxidant, aldehyde as a raw material, and ferric nitrate as a catalyst to oxidize the raw material aldehyde to generate acid and peroxyacid. The method of the present invention can selectively oxidize alcohols or aldehydes containing carbon-carbon single bonds, carbon-carbon double bonds, carbon-carbon triple bonds, halogens, ester groups and other functional groups by pure oxygen or air under normal pressure. Alcohols are oxidized to the corresponding acids. The invention has many advantages such as mild reaction conditions, high yield, simple operation, convenient separation and purification, good substrate functional group compatibility, energy saving, greenness, and environmental friendliness, and is a method suitable for industrial production.

The invention has the advantage of wide substrate universality, and can be used to catalyze and oxidize common alcohols, and can also be used to catalyze and oxidize alcohols with complex structures, such as ester groups, ethers, halogens, benzene rings, heterocycles, alkynyl groups, double bonds Alcohols and other functional groups, and even terpenes and steroid structures are also compatible under the conditions of the present invention, and are suitable for the field of drug research and development. The invention has the advantages of high yield, mild reaction conditions, simple operation, convenient separation and purification, and the like. The invention overcomes the defects in the prior art of using equivalent heavy metals as oxidants or noble metals as catalysts, relatively harsh reaction conditions, poor compatibility of substrate functional groups, high temperature and high pressure required for the reaction, and the like. The method of the present invention can be used for small-scale laboratory synthesis and also suitable for large-scale industrial production.

The invention uses cheap and widely sourced oxygen or air as the oxidizing agent to replace the chemical oxidizing agent used in the traditional oxidizing agent system. The catalysts used are ferric nitrate, TEMPO and inorganic halides, all of which are readily available in industry. Since the catalytic oxidation condition of the present invention is very mild, it can be carried out only under room temperature, normal pressure and neutral conditions, and the operation is very convenient and easy to control. Since the oxidizing agent used in the reaction process is oxygen or air, and the by-product is water, the whole reaction process hardly causes any pollution to the environment, and it is a green chemical synthesis method. The invention has simple post-processing, high product yield and can effectively reduce production and manufacturing costs.

Under the conditions of the present invention, diols can form lactones or diacids. Specifically, some 1,4-diols and 1,5-diols can form lactones. And 1,8-diols can generate diacids. This also provides a green and low-cost new method for the synthesis of lactone and diacid products.

The invention also proposes the application of the acid in laboratory preparation, drug synthesis and industrial production.

The invention also proposes the application of the diacid in laboratory preparation, drug synthesis and industrial production.

The invention also proposes the application of the lactone in laboratory preparation, drug synthesis and industrial production.

The present invention also proposes a method for synthesizing (R _a )-7,8-eicosenoic acid (phlomic acid) shown in formula (I), said method comprising:

(1) Using 7-octyn-1-ol as raw material, ferric nitrate, 2,2,6,6-tetramethylpiperidine nitrogen oxide, and inorganic halides as catalysts, an oxidation reaction occurs to obtain 7-octyne acid;

(2) carry out methylation reaction to the 7-octynoic acid prepared in step (1), obtain 7-octynoic acid methyl ester;

(3) The 7-octynoic acid methyl ester prepared by copper bromide and dimethylprolinol catalytic step (2) undergoes EATA reaction (asymmetric allenyl reaction of alkynes) to obtain allenoic acid methyl ester ;

(4) In the presence of potassium hydroxide, in a methanol/water system, hydrolyze the allenoic acid methyl ester prepared in step (3) to obtain the axial chiral allenoic acid (R _a )-7 shown in formula (I), 8-Eicosenoic acid.

Wherein, the method for preparing 7-octynoic acid in the step (1) is the method for preparing acid by oxygen oxidation of alcohol or aldehyde proposed in the present invention, and the raw material is 7-octyn-1-ol.

Described reaction process is shown in route (a):

In a specific experimental scheme, as shown in reaction formula (i), dodecanol 3a is used as raw material, ferric nitrate (Fe(NO ₃ ) ₃ 9H ₂ O), 2,2,6,6-tetra When methylpiperidine nitrogen oxide and KCl were used as catalysts, the content of alcohol, aldehyde and acid in the reaction was monitored by NMR internal standard method. Wherein, when the consumption of KCl is 10mol%, at first generate initial product dodecanal 1a, after 2 hours, generate dodecanoic acid 2a, dodecyl alcohol is consumed completely (as shown in Figure 2A) in six hours; And with 10mol%NaCl When 10 mol% of KCl was replaced, dodecanol could not generate dodecanoic acid 2a within 4 hours (as shown in FIG. 2B ).

Description of drawings

Fig. 1 is the schematic diagram of reaction mechanism of the present invention.

Among Fig. 2, Fig. 2A shows that the product dodecanoic acid is generated from the raw material dodecanol when KCl is used as the catalyst in the present invention; Fig. 2B shows that the product dodecanoic acid is generated from the raw material dodecanol when NaCl is used as the catalyst in the present invention.

detailed description

The present invention will be further described in detail in conjunction with the following specific embodiments and accompanying drawings. The process, conditions, experimental methods, etc. for implementing the present invention, except for the content specifically mentioned below, are common knowledge and common knowledge in this field, and the present invention has no special limitation content.

Embodiment 1: the synthesis of dodecanoic acid

Among them, rt is room temperature.

Under an oxygen atmosphere (oxygen balloon), Fe(NO ₃ ) ₃ ·9H ₂ O (40.4mg, 0.10mmol), 2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO, 15.5mg, 0.10 mmol), KCl (7.5 mg, 0.10 mmol), dodecanol (189.0 mg, 98% purity, 1.0 mmol) and 1,2-dichloroethane (DCE, 4 mL) were added to a 50 mL Schlenk tube. Stir at room temperature for 12 h, and monitor by TLC until the reaction is complete. The reaction solution was filtered through a short column of silica gel, rinsed with ether (75 mL), and concentrated to obtain a crude product. The crude product was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the corresponding dodecanoic acid (199.2 mg, 100%). ¹ H NMR (400MHz, CDCl ₃ ) δ11.68 (brs, 1H, COOH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.39-1.21 (m, 16H, 8×CH ₂ ), 0.88 (t, J=7.0Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.7, 34.1, 31.9, 29.6, 29.4, 29.3, 29.2, 29.0, 24.6, 22.7, 14.1.

Embodiment 2: the synthesis of octanoic acid

Other operations refer to Example 1, the raw material used is octanol, and the reaction time is 12 hours to obtain octanoic acid (122.1 mg, 85%). ¹ H NMR (400MHz, CDCl ₃ ) δ11.47 (brs, 1H, COOH), 2.35 (t, J=7.4Hz, 2H, CH ₂ ), 1.63 (quint, J=7.4Hz, 2H, CH ₂ ), 1.39-1.21 (m, 8H, 4×CH ₂ ), 0.88 (t, J=7.0Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl3) δ180.6, 34.1, 31.6, 29.0, 28.9, 24.6 , 22.6, 14.0.

Embodiment 3: the synthesis of phenylpropionic acid

Other operations refer to Example 1, the raw material used is phenylpropanol (138.4mg, 98% purity, 1.0mmol), and the reaction time is 12 hours to obtain phenylpropionic acid (147.1mg, 98%). ¹ H NMR (400MHz, CDCl ₃ ) δ11.48 (brs, 1H, COOH), 7.33-7.15 (m, 5H, Ar-H), 2.95 (t, J=8.0Hz, 2H, CH ₂ ), 2.67 ( t, J=7.8Hz, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ179.6, 140.1, 128.5, 128.2, 126.3, 35.6, 30.5.

Embodiment 4: the synthesis of hexadecanoic acid

Other operations refer to Example 1, the raw material used is cetyl alcohol (247.4 mg, 98% purity, 1.0 mmol), and the reaction time is 12 hours to obtain cetyl acid (254.2 mg, 99%). Melting point: 62-63°C (petroleum ether/ethyl acetate=100/1 recrystallization) (literature value: 62.2–63.3°C); ¹ H NMR (400MHz, CDCl ₃ ) δ11.60 (brs, 1H, COOH), 2.35(t, J=7.4Hz, 2H, CH ₂ ), 1.63(quint, J=7.4Hz, 2H, CH ₂ ), 1.38-1.19(m, 24H, 12×CH ₂ ), 0.88(t, J= 6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.7, 34.1, 31.9, 29.71, 29.69, 29.68, 29.66, 29.65, 29.60, 29.44, 29.37, 29.2, 29.1, 24.7, 22.7, 14.1; IR (neat, cm ^-1 ): 3300-2300, 1698, 1471, 1430, 1310, 1293, 1271, 1250, 1228, 1207, 1188; MS (EI) m/z (%): 256 (M ⁺ ,60.14),73(100).

Example 5: Synthesis of 6-methoxyl-6-oxoylhexanoic acid

Other operations refer to Example 1, the raw material used is methyl 6-hydroxyhexanoate (146.5 mg, 1.0 mmol), and the reaction time is 12 hours to obtain 6-methoxy-6-oxohexanoic acid (138.4 mg, 94%) (petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ9.21 (brs, 1H, COOH), 3.68 (s, 3H, CH ₃ ), 2.43-2.31 (m, 4H, 2×CH ₂ ), 1.75-1.62 (m, 4H, 2×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ179.4, 173.8, 51.6, 33.6, 24.2, 24.0; IR (neat, cm ^-1 ): 3400-2700, 1736, 1707, 1438, 1416, 1367, 1259, 1199, 1175, 1143, 1080, 1016. MS (ESI, Neg) m/z (%): 159 (M-1) ^- .

Example 6: Synthesis of 8-acetoxy octanoic acid

Other operations refer to Example 1, the raw material used is 8-acetoxy octanol (187.8 mg, 1.0 mmol), and the reaction time is 12 hours to obtain 8-acetoxy octanoic acid (188.3 mg, 93%) (petroleum ether: acetic acid ethyl ester = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ9.58 (brs, 1H, COOH), 4.05 (t, J = 6.6Hz, 2H, CH ₂ ), 2.35 (t, J = 7.4Hz, 2H, CH ₂ ), 2.05(s,3H,CH ₃ ),1.69-1.57(m,4H,2×CH ₂ ),1.42-1.30(m,6H,3×CH ₂ ); ¹³ C NMR(100MHz,CDCl ₃ )δ179.9,171.4 ,64.5,33.9,28.81,28.78,28.4,25.6,24.5,20.9; IR(neat,cm ^-1 ):3600-2400,1706,1464,1413,1391,1366,1234,1100,1036; MS(EI) m/z(%):202(M ⁺ ,2.51),55(100).

Embodiment 7: the synthesis of tetrahydrofuran-2-carboxylic acid

Other operations refer to Example 1, the raw material used is tetrahydrofuran-2-methanol (103.7 mg, 99% purity, 1.0 mmol), and the reaction time is 12 hours to obtain tetrahydrofuran-2-carboxylic acid (82.0 mg, 70%) (petroleum ether: Ethyl acetate = 5:1 to 2:1). ¹ HNMR (400MHz, CDCl ₃ ) δ9.82 (brs, 1H, COOH), 4.52 (dd, J ₁ = 8.6Hz, J ₂ = 5.4Hz, 1H, CH), 4.09-4.00 (m, 1H, one proton of CH ₂ ),3.99-3.90(m,1H,one proton of CH ₂ ),2.38-2.27(m,1H,one proton of CH ₂ ),2.16-2.06(m,1H,one proton of CH ₂ ); 2.04-1.89 (m, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ177.8, 76.2, 69.6, 30.1, 25.2; IR (neat, cm ^-1 ): 3400-2600, 1722, 1449, 1411, 1351, 1310, 1203, 1176, 1072, 1037; MS (EI) m/z (%): 116 (M ⁺ , 1.09), 71 (100).

Embodiment 8: the synthesis of thiophene-2-acetic acid

Other operations refer to Example 1, the raw material used is thiophene-2-ethanol (130.7 mg, 98% purity, 1.0 mmol), and the reaction time is 12 hours to obtain thiophene-2-acetic acid (120.1 mg, 85%) (petroleum ether: Ethyl acetate=5:1 to 2:1) (132.0 mg, 1.0 mmol), the reaction time was 2.3 hours to obtain thiophene-2-acetic acid (111.9 mg, 86%). Melting point: 61.3-62.4°C (petroleum ether/ethyl acetate recrystallization) (literature value: 61-62.5°C); ¹ H NMR (400MHz, CDCl ₃ ) δ10.89 (brs, 1H, COOH), 7.24-7.20 ( m,1H,Ar-H),6.98-6.94(m,2H,Ar-H),3.87(s,2H,CH ₂ ); ¹³ C NMR(100MHz,CDCl ₃ )δ177.0,134.0,127.2 126.9,125.3, 35.0; IR (neat, cm ^-1 ): 3300-2300, 1692, 1438, 1417, 1399, 1362, 1331, 1222, 1188, 1148, 1128, 1081, 1040; MS (EI) m/z (%): 142(M ⁺ ,48.52),97(100).

Example 9: Synthesis of 9-bromo-1-nonanoic acid

Other operations refer to Example 1, the raw material used is 9-bromo-1-nonanol (228.0mg, 98% purity, 1.0mmol), and the reaction time is 12 hours to obtain 9-bromo-1-nonanoic acid (232.6mg, 98 %) (petroleum ether: ethyl acetate = 5:1 to 3:1). Melting point: 35.3-36.5°C (petroleum ether/ethyl acetate recrystallization) (literature value: 35-36.5°C); ¹ H NMR (400MHz, CDCl ₃ ) δ11.54(brs,1H,COOH),3.41(t, J=6.8Hz, 2H, CH ₂ ), 2.36(t, J=7.6Hz, 2H, CH ₂ ), 1.85(quint, J=7.2Hz, 2H, CH ₂ ), 1.63(quint, J=7.3Hz, 2H, CH ₂ ), 1.48-1.28 (m, 8H, 4×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.4, 34.0, 33.9, 32.7, 29.0, 28.8, 28.5, 28.0, 24.5; IR (neat,cm ^-1 ):3100-2500,1689,1468,1427,1406,1338,1303,1275,1241,1211,1188,1097,1043; MS(EI)m/z(%):238(M ( ⁸¹ Br) ⁺ ,1.16),236(M( ⁷⁹ Br) ⁺ ,1.16),60(100).

Embodiment 10: the synthesis of 2-hexyloxyacetic acid

Other operations refer to Example 1, the raw material used is 2-hexyloxyethanol (149.8mg, 98% purity, 1.0mmol), and the reaction time is 12 hours to obtain 2-hexyloxyacetic acid (147.7mg, 92%) (petroleum ether:ethyl acetate=5:1 to 2:1). ¹ HNMR (400MHz, CDCl ₃ ) δ10.14 (brs, 1H, COOH), 4.13 (s, 2H, CH ₂ ), 3.56 (t, J=6.8Hz, 2H, CH ₂ ), 1.67-1.59 (m, 2H, CH ₂ ), 1.41-1.24 (m, 6H, 3×CH ₂ ), 0.88 (t, J=7.0Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ175.6, 72.1, 67.6,31.5,29.3,25.5,22.5,13.9.IR(neat,cm ^-1 ):3600-2500,2930,2862,1729,1462,1431,1239,1126,298,807,727,676; MS(EI)m/z(% ):160(M ⁺ ,2.82),83(100).

Example 11: Synthesis of 7-octynoic acid

Other operations refer to Example 1, the raw material used is 7-alkyne-1-octanol (126.0mg, 1.0mmol), and the reaction time is 12 hours to obtain 7-octynoic acid (111.7mg, 80%) (petroleum ether: acetic acid ethyl ester = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.41 (brs, 1H, COOH), 2.38 (t, J = 7.4Hz, 2H, CH ₂ ), 2.20 (td, J ₁ = 6.9Hz, J ₂ = 2.5Hz ,2H,≡CCH ₂ ), 1.95(t,J=2.6Hz,2H,≡CH),1.71-1.61(m,2H,CH ₂ ),1.60-1.42(m,4H,2×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.3, 84.2, 68.4, 33.9, 28.02, 27.98, 24.1, 18.2.

Example 12: Synthesis of 4-pentynoic acid

Other operations refer to Example 1, the raw material used is 4-pentyn-1-alcohol (89.3mg, 95% purity, 1.0mmol), and the reaction time is 12 hours to obtain 4-pentynoic acid (59.3mg, 60%) ( Petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.29 (brs, 1H, COOH), 2.66-2.60 (m, 2H, CH ₂ ), 2.56-2.48 (m, 2H, CH ₂ ), 2.01 (t, J= 2.8Hz, 1H, ≡CH); ¹³ C NMR (100MHz, CDCl ₃ ) δ178.2, 82.1, 69.2, 33.1, 14.0.

Example 13: Synthesis of 10-undecynoic acid

Other operations refer to Example 1, the raw material used is 10-undecyn-1-alcohol (182.6mg, 1.0mmol), and the reaction time is 12 hours to obtain 10-undecynoic acid (186.5mg, 95%) (petroleum ether :ethyl acetate=5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.18 (brs, 1H, COOH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 2.15-2.08 (m, 2H, CH ₂ ), 1.78 (t , J=2.6Hz, 3H, CH ₃ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.46 (quint, J=7.2Hz, 2H, CH ₂ ), 1.41-1.24 (m, 8H, 4×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.5, 79.3, 75.3, 34.1, 29.1, 28.98, 28.95, 28.91, 28.8, 24.6, 18.7, 3.4.

Example 14: Synthesis of 3-trimethylsilylpropiolic acid

Other operations refer to Example 1, the raw material used is 3-trimethylsilyl propynol (128.8 mg, 1.0 mmol), and the reaction time is 36 hours to obtain 3-trimethylsilyl propiolic acid (93.7 mg, 66 %) (petroleum ether: ethyl acetate=5:1). ¹ HNMR (400MHz, CDCl ₃ ) δ9.91 (brs, 1H, COOH), 0.26 (s, 9H, 3×CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ 157.6, 97.4, 93.8, -1.0 ; IR (neat, cm ^-1 ): 3600-2500, 2964, 2176, 1687, 1400, 1252, 913, 840, 760; MS (EI) m/z (%): 142 (M ⁺ , 12.82), 75 (100).

Example 15: Synthesis of cyclohex-3-ene-1-carboxylic acid

Other operations refer to Example 1, the raw material used is cyclohex-3-ene-1-methanol (114.7mg, 98% purity, 1.0mmol), and the reaction time is 48 hours to obtain cyclohex-3-ene-1-carboxylic acid ( 102.5mg, 81%) (petroleum ether: ethyl acetate = 5:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.01 (brs, 1H, COOH), 5.74-5.64 (m, 2H, CH=CH), 2.65-2.56 (m, 1H, CH), 2.35-2.25 (m, 2H,CH ₂ ),2.20-1.99(m,3H,CH ₂ ),1.78-1.65(m,1H,CH ₂ ); ¹³ CNMR(100MHz,CDCl ₃ )δ182.5,126.6,124.8,39.0,27.0,24.7, 24.2. MS (EI) m/z (%): 126 (M ⁺ , 27.78), 79 (100).

Example 16: Synthesis of suberic acid

Other operations refer to Example 1, the raw material used is octane glycol (149.8mg, 98% purity, 1.0mmol), the reaction time is 48 hours, obtain suberic acid (150.8mg, 86%) (ethyl acetate/n-hexane weight crystallization). Melting point: 138.6-139.7°C (literature value: 144°C); ¹ H NMR (400MHz, DMSO-d ₆ ) δ12.00(s, 3H, CH ₃ ), 2.19(t, J=7.2Hz, 4H, 2× CH ₂ ), 1.54-1.42 (m, 4H, 2×CH ₂ ), 1.31-1.20 (m, 4H, 2×CH ₂ ); ¹³ C NMR (100MHz, d ⁶ -DMSO) δ174.5, 33.6, 28.3 ,24.4.IR(neat,cm ^-1 ):3500-2200,1688,1466,1408,1332,1252,1190,1065,1011.MS(EI)m/z(%):174(M ⁺ ,0.23) ,138(100).

Example 17: Synthesis of (+)-sclereolactone

Other operations refer to Example 1, the raw material used is sclarediol (254.4 mg, 1.0 mmol), and the reaction time is 12 hours to obtain (+)-sclera lactone (230.1 mg, 92%) (petroleum ether: ethyl acetate = 20:1 to 5:1). Melting point: 123.7-124.5°C (petroleum ether/ethyl acetate recrystallization) (literature value: 121-124°C); specific optical rotation [α] _D ^28.7 = 47.9 (c=1.01, CHCl ₃ ) (literature value: [α] _D ²⁰ =47 (c=1.01, CHCl ₃ )); ¹ H NMR (400MHz, CDCl ₃ ) δ2.41 (dd, J ₁ =16.0Hz, J ₂ =14.8Hz, 1H, one proton of CH ₂ ), 2.23 (dd, J ₁ =16.4Hz, J ₂ =6.4Hz, 1H, CH ₂ ), 2.08 (dt, J ₁ =11.6Hz, J ₂ =3.2Hz, 1H), 1.97 (dd, J ₁ =14.8Hz ,J ₂ =6.6Hz,1H,CH ₂ ),1.92-1.84(m,1H,CH ₂ ),1.74-1.60(m,2H,CH ₂ ),1.50-1.31(m,7H),1.20(dt, J ₁ =14.0Hz, J ₂ =4.0Hz, 1H, CH ₂ ), 1.10-1.00(m, 2H), 0.91(s, 3H, CH ₃ ), 0.89(s, 3H, CH ₃ ), 0.84(s , 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ176.8, 86.3, 59.0, 56.5, 42.0, 39.3, 38.6, 35.9, 33.05, 32.99, 28.6, 21.4, 20.8, 20.4, 18.0, 14.9; IR (neat, cm ^-1 ): 2928, 2897, 2869, 1766, 1460, 1390, 1223, 1178, 1122, 1017; MS (EI) m/z (%): 250 (M ⁺ , 3.96), 123 ( 100).

Example 18: Synthesis of 3-oxo-5β-cholanic acid

Other operations refer to Example 1, the raw material used is (3α,5β)-3,24-cholanediol (362.6mg, 1.0mmol), and the reaction time is 24 hours to obtain 3-carbonyl-5β-cholanic acid (272.4mg ,73%) (petroleum ether: ethyl acetate = 2:1). Melting point: 139.9-142.1°C (petroleum ether/ethyl acetate recrystallization) (literature value: 137.7°C); specific optical rotation [α] _D ^25.3 = 28.7 (c=1.02, CHCl ₃ ) (literature value: [α] _D ^25.3 =28.1 (c=0.01, CHCl ₃ )); ¹ H NMR (400MHz, CDCl ₃ ) δ11.45 (brs, 1H, COOH), 2.70 (t, J=14.2Hz, 1H, CH ₂ ), 2.46-2.22 (m,3H),2.21-2.13(m,1H),2.08-1.98(m,3H),1.94-1.76(m,4H),1.65-1.55(m,1H),1.55-1.04(m,15H) ,1.02(s,3H,CH ₃ ),0.93(d,J=6.4Hz,3H,CH ₃ ),0.69(s,3H,CH ₃ ); ¹³ C NMR(100MHz,CDCl ₃ )δ213.9,180.4,56.3 , ^{55.8,44.2,42.7,42.2,40.5,39.9,37.1,36.9,35.4,35.2,34.8,31.0,30.6,28.1,26.5,25.7,24.1,22.6,21.1,18.2,12.0} . ):3400-2500,1699,1448,1412,1380,1304,1262,1225,1182,1099. MS(EI) m/z(%):374(M ⁺ ,12.22),55(100).

Embodiment 19: Synthesis of phthalide

Other operations refer to Example 1, the raw material used is phthalic glycol (141.3mg, 98% purity, 1.0mmol), and the reaction time is 12 hours to obtain phthalide (82.7mg, 62%) (petroleum ether: ethyl acetate = 15:1 to 10:1). Melting point: 72.0-73.4°C (petroleum ether/ethyl acetate recrystallization) (literature value: 72-74°C). ¹ H NMR (400MHz, CDCl ₃ ) δ7.94 (d, J=7.6Hz, 1H, Ar- _{13 _ _} ^_ C NMR (100MHz, CDCl ₃ ) δ171.0, 146.5, 133.9, 128.9, 125.6, 125.6, 122.1, 69.6; IR (neat, cm ^-1 ): 2944, 2924, 1745, 1615, 1593, 1466, 1436, 1364, 1317 ,1286,1191,1108,1047; MS (EI) m/z (%): 134 (M ⁺ ,46.06), 105 (100).

Example 20: Synthesis of Dodecanoic Acid (Air Oxidation)

Fe(NO ₃ ) ₃ 9H ₂ O (40.5 mg, 0.1 mmol) and DCE (4.0 mL) were added to a 100 mL round bottom flask, followed by TEMPO (15.7 mg, 0.1 mmol), KCl (7.8 mg, 0.1 mmol) , dodecyl alcohol (189.3 mg, 98% purity, 1.0 mmol) and DCE (1.0 mL). The round bottom bottle is connected to an air balloon through a pumping valve. The reaction was stirred at room temperature for 16 hours until the reaction was completed as monitored by TLC (petroleum ether:ethyl acetate=5:1). The reaction mixture was filtered through a short column of crude silica gel, rinsed with diethyl ether (75mL). After the solvent was spin-dried in vacuo, silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) was purified to obtain dodecanoic acid (189.7mg, 95%) . ¹ HNMR (400MHz, CDCl ₃ ) δ11.68 (brs, 1H, COOH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.39 -1.21(m,16H,8×CH ₂ ),0.88(t,J=6.8Hz,3H,CH ₃ ); ¹³ CNMR(100MHz,CDCl ₃ )δ180.7,34.1,31.9,29.6,29.4,29.3, 29.2, 29.0, 24.6, 22.7, 14.1. IR (neat, cm ^-1 ): 3400-2500, 1694, 1466, 1429, 1351, 1301, 1278, 1247, 1218, 1192; MS (EI) m/z (% ):200(M ⁺ ,21.87),73(100).

Example 21: Synthesis of octanoic acid (air oxidation)

Other operations refer to Example 20, the raw material used is octanol (132.0 mg, 99% purity, 1.0 mmol), and the reaction time is 16 hours to obtain octanoic acid (128.6 mg, 89%) (petroleum ether: ethyl acetate=5:1 ). ¹ H NMR (400MHz, CDCl ₃ ) δ10.26 (brs, 1H, COOH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 1.63 (quint, J=7.4Hz, 2H, CH ₂ ), 1.39-1.22 (m, 8H, 4×CH ₂ ), 0.88 (t, J=6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.5, 34.1, 31.6, 29.0, 28.9, 24.6, 22.6, 14.0; IR (neat, cm ^-1 ): 2925, 2857, 1707, 1462, 1413, 1277, 1231, 1203, 1109, 933, 725; MS (EI) m/z (%): 144 (M ⁺ ,3.74),60(100).

Embodiment 22: the synthesis of phenylpropionic acid

Other operations refer to Example 20, the raw material used is phenylpropanol (138.6mg, 98% purity, 1.0mmol), and the reaction time is 16 hours to obtain phenylpropionic acid (149.0mg, 99%) (petroleum ether: ethyl acetate = 5:1 to 2:1). Melting point: 46.6-47.6°C (petroleum ether/ethyl acetate recrystallization); ¹ H NMR (400MHz, CDCl ₃ ) δ10.35 (brs, 1H, COOH), 7.33-7.16 (m, 5H, Ar-H), 2.95 (t, J=7.8Hz, 2H, CH ₂ ), 2.68 (t, J=7.8Hz, 2H, CH ₂ ); ¹³ C NMR (100 MHz, CDCl ₃ ) δ179.4, 140.1, 128.5, 128.2, 126.3, 35.6 ,30.5; IR(neat,cm ^-1 ):3400-2400,1693,1448,1427,1300,1216,928,785,753,723,698; MS(EI)m/z(%):150(M ⁺ ,38),91(100 ).

Example 23: Synthesis of Hexadecanoic Acid

Other operations refer to Example 20, the raw material used is cetyl alcohol (247.0 mg, 98% purity, 1.0 mmol), and the reaction time is 16 hours to obtain cetyl acid (250.5 mg, 98%). ¹ H NMR (400MHz, CDCl ₃ ) δ11.43 (brs, 1H, COOH), 2.35 (t, J=7.4Hz, 2H, CH ₂ ), 1.63 (quint, J=7.4Hz, 2H, CH ₂ ), 1.36-1.21 (m, 24H, 12×CH ₂ ), 0.88 (t, J=6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.6, 34.1, 31.9, 29.70, 29.68, 29.66, 29.65, 29.60, 29.44, 29.37, 29.2, 29.1, 24.7, 22.7, 14.1.

Example 24: Synthesis of 6-methoxy-6-oxohexanoic acid

Other operations refer to Example 20, the raw material used is methyl 6-hydroxyhexanoate (146.5 mg, 1.0 mmol), and the reaction time is 16 hours to obtain 6-methoxy-6-oxohexanoic acid (138.2 mg, 86%) (petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ9.10 (brs, 1H, COOH), 3.68 (s, 3H, CH ₃ ), 2.43-2.30 (m, 4H, 2×CH ₂ ), 1.75-1.62 (m, 4H, 2×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ179.3, 173.8, 51.6, 33.6, 24.2, 24.0.

Example 25: Synthesis of 8-acetoxyoctanoic acid

Other operations refer to Example 20, the raw material used is 8-acetoxyoctanol (187.7mg, 1.0mmol), and the reaction time is 16 hours to obtain 8-acetoxyoctanoic acid (188.9mg, 93%) (petroleum ether: acetic acid ethyl ester = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ10.62 (brs, 1H, COOH), 4.05 (t, J = 6.6Hz, 2H, CH ₂ ), 2.35 (t, J = 7.6Hz, 2H, CH ₂ ), 2.05(s,3H,CH ₃ ),1.69-1.57(m,4H,2×CH ₂ ),1.42-1.30(m,6H,3×CH ₂ ); ¹³ C NMR(100MHz,CDCl ₃ )δ180.0,171.4 ,64.5,33.9,28.82,28.78,28.4,25.6,24.5,20.9.

Example 26: Synthesis of tetrahydrofuran-2-carboxylic acid

Other operations refer to Example 20, the raw material used is tetrahydrofuran-2-methanol (103.0 mg, 99% purity, 1.0 mmol), and the reaction time is 16 hours to obtain tetrahydrofuran-2-carboxylic acid (85.0 mg, 73%) (petroleum ether: Ethyl acetate = 5:1 to 2:1). ¹ HNMR (400MHz, CDCl ₃ ) δ9.74 (brs, 1H, COOH), 4.51 (dd, J ₁ = 8.6Hz, J ₂ = 5.4Hz, 1H, CH), 4.09-4.01 (m, 1H, one proton of CH ₂ ),3.99-3.91(m,1H,one proton of CH ₂ ),2.38-2.27(m,1H,one proton of CH ₂ ),2.17-2.06(m,1H,one proton of CH ₂ ); 2.04-1.89 (m, 2H, CH ₂ ); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 177.8, 76.3, 69.6, 30.1, 25.2.

Example 27: Synthesis of thiophene-2-acetic acid

Other operations refer to Example 20, the raw material used is thiophene-2-ethanol (130.5 mg, 98% purity, 1.0 mmol), and the reaction time is 16 hours to obtain thiophene-2-acetic acid (114.7 mg, 81%) (petroleum ether: Ethyl acetate = 5:1 to 2:1) (132.0 mg, 1.0 mmol). ¹ H NMR (400MHz, CDCl ₃ )δ10.90(brs,1H,COOH),7.25-7.21(m,1H,Ar-H),6.98-6.93(m,2H,Ar-H),3.87(s, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ177.0, 133.9, 127.2126.9, 125.3, 35.0.

Example 28: Synthesis of 9-bromo-1-nonanoic acid

Other operations refer to Example 20, the raw material used is 9-bromo-1-nonanol (228.0mg, 98% purity, 1.0mmol), and the reaction time is 16 hours to obtain 9-bromo-1-nonanoic acid (233.5mg, 98 %) (petroleum ether: ethyl acetate = 5:1 to 3:1). ¹ HNMR (400MHz, CDCl ₃ ) δ11.59 (brs, 1H, COOH), 3.41 (t, J = 6.8Hz, 2H, CH ₂ ), 2.35 (t, J = 7.4Hz, 2H, CH ₂ ), 1.85 (quint, J=7.2Hz, 2H, CH ₂ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.48-1.27 (m, 8H, 4×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.5, 34.0, 33.9, 32.7, 29.0, 28.9, 28.5, 28.0, 24.5.

Example 29: Synthesis of 2-hexyloxyacetic acid

Other operations refer to Example 20, the raw material used is 2-hexyloxyethanol (148.5mg, 98% purity, 1.0mmol), and the reaction time is 16 hours to obtain 2-hexyloxyacetic acid (147.7mg, 84%) (petroleum ether:ethyl acetate=5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ8.83 (brs, 1H, COOH), 4.12 (s, 2H, CH ₂ ), 3.56 (t, J=6.6Hz, 2H, CH ₂ ), 1.68-1.58 (m ,2H,CH ₂ ),1.41-1.24(m,6H,3×CH ₂ ),0.88(t,J=6.8Hz,3H,CH ₃ ); ¹³ CNMR(100MHz,CDCl ₃ )δ175.7,72.1, 67.6, 31.5, 29.3, 25.5, 22.5, 13.9.

Example 30: Synthesis of 7-octynoic acid

Other operations refer to Example 20, the raw material used is 7-alkyne-1-octanol (126.2 mg, 1.0 mmol), and the reaction time is 16 hours to obtain 7-octynoic acid (112.2 mg, 80%) (petroleum ether: acetic acid ethyl ester = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.01 (brs, 1H, COOH), 2.38 (t, J = 7.6Hz, 2H, CH ₂ ), 2.21 (td, J ₁ = 6.9Hz, J ₂ = 2.5Hz ,2H,≡CCH ₂ ), 1.95(t,J=2.6Hz,1H,≡CH),1.71-1.62(m,2H,CH ₂ ),1.61-1.42(m,4H,2×CH ₂ ); ¹³ C NMR(100MHz, CDCl ₃ )δ180.1,84.2,68.4,33.9,28.04,27.99,24.1,18.2. IR(neat)ν(cm ^-1 )3298,2940,2864,2117,1707,1461,1413, 1278, 1225, 1141, 1085; MS (ESI, Neg) m/z (%): 139 (M-1) ^- .

Example 31: Synthesis of 4-pentynoic acid

Other operations refer to Example 20, the raw material used is 4-pentyn-1-ol (89.1mg, 95% purity, 1.0mmol), and the reaction time is 16 hours to obtain 4-pentynoic acid (67.0mg, 68%) ( Petroleum ether: ethyl acetate = 5:1 to 2:1). Melting point: 55.9-57.0°C (petroleum ether/ethyl acetate recrystallization); ¹ H NMR (400MHz, CDCl ₃ ) δ11.37 (brs, 1H, COOH), 2.66-2.60 (m, 2H, CH ₂ ), 2.56 -2.49(m,2H,CH ₂ ),2.01(t,J=2.6Hz,1H,≡CH); ¹³ C NMR(100MHz,CDCl ₃ )δ178.3,82.0,69.2,33.1,14.0.IR(neat )ν(cm ^-1 )3500-2000,3276,2927,2627,2119,1694,1426,1353,1299,1217,1024,890.MS(EI)m/z(%):98(M ⁺ ,3.7 ),70(100)

Example 32: Synthesis of 10-undecynoic acid

Other operations refer to Example 20, the raw material used is 10-undecyn-1-alcohol (182.8 mg, 1.0 mmol), and the reaction time is 16 hours to obtain 10-undecynoic acid (176.2 mg, 90%) (petroleum ether :ethyl acetate=5:1 to 2:1). Melting point: 51.3-52.2°C (petroleum ether/ethyl acetate recrystallization); ¹ H NMR (400MHz, CDCl ₃ ) δ9.57 (brs, 1H, COOH), 2.35 (t, J = 7.6Hz, 2H, CH ₂ ), 2.15-2.08 (m, 2H, CH ₂ ), 1.78 (t, J = 2.6Hz, 3H, CH ₃ ), 1.63 (quint, J = 7.3Hz, 2H, CH ₂ ), 1.46 (quint, J = 7.1Hz, 2H, CH ₂ ), 1.41-1.24 (m, 8H, 4×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.4, 79.3, 75.3, 34.1, 29.1, 28.98, 28.96, 28.91, ⁽ %): 196(M ⁺ , 0.57), 68(100).

Example 33: Synthesis of 3-trimethylsilylpropiolic acid

Other operations refer to Example 20, the raw material used is 3-trimethylsilyl propynyl alcohol (128.6 mg, 1.0 mmol), and the reaction time is 48 hours to obtain 3-trimethylsilyl propiolic acid (92.9 mg, 65 %) (petroleum ether: ethyl acetate=5:1). ¹ HNMR (400MHz, CDCl ₃ ) δ6.78 (brs, 1H, COOH), 0.26 (s, 9H, 3×CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ 157.4, 97.4, 93.7, -1.0 .

Example 34: Synthesis of cyclohex-3-ene-1-carboxylic acid

Other operations refer to Example 20, the raw material used is cyclohex-3-ene-1-methanol (115.9 mg, 98% purity, 1.0 mmol), and the reaction time is 48 hours to obtain cyclohex-3-ene-1-carboxylic acid ( 89.9 mg, 70%) (petroleum ether: ethyl acetate = 5:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.63 (brs, 1H, COOH), 5.75-5.60 (m, 2H, CH ₂ ), 2.68-2.55 (m, 1H, CH), 2.36-2.00 (m, 5H , CH ₂ ), 1.78-1.65 (m, 1H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ182.7, 126.7, 124.9, 39.1, 27.1, 24.8, 24.3.

Example 35: Synthesis of suberic acid

Other operations refer to Example 20, the raw material used is octane diol (148.8mg, 98% purity, 1.0mmol), and the reaction time is 48 hours to obtain suberic acid (144.4mg, 83%) (ethyl acetate/n-hexane weight crystallization). ¹ H NMR (400MHz, DMSO-d ₆ ) δ12.00(s, 3H, CH ₃ ), 2.19(t, J=7.4Hz, 4H, 2×CH ₂ ), 1.54-1.41(m, 4H, 2× CH ₂ ), 1.31-1.21 (m, 4H, 2×CH ₂ ); ¹³ C NMR (100MHz, d ⁶ -DMSO) δ174.5, 33.6, 28.3, 24.4.

Example 35: Synthesis of (+)-sclereolactone

Other operations refer to Example 20, the raw material used is sclarediol (254.8 mg, 1.0 mmol), and the reaction time is 16 hours to obtain (+)-sclera lactone (233.5 mg, 93%) (petroleum ether: ethyl acetate = 20:1 to 5:1). Specific rotation [α] _D ^28.7 = 46.9 (c = 1.00, CHCl ₃ ) (literature value: [α] _D ²⁰ = 47 (c = 1.01, CHCl ₃ )); ¹ H NMR (400MHz, CDCl ₃ ) δ2.41 (dd, J ₁ =15.6Hz, J ₂ =15.6Hz, 1H, CH ₂ ), 2.23(dd, J ₁ =15.0Hz, J ₂ =6.4Hz, 1H, CH ₂ ), 2.08(dt, J ₁ = _{( _ _ _ _} m,2H,CH ₂ ),1.50-1.31(m,7H),1.20(dt,J ₁ =13.5Hz,J ₂ =4.3Hz,1H,CH ₂ ),1.10-1.00(m,2H),0.91( s,3H,CH ₃ ),0.89(s,3H,CH ₃ ),0.84(s,3H,CH ₃ ); ¹³ C NMR(100MHz,CDCl ₃ )δ176.7,86.2,59.0,56.5,42.0,39.4 ,38.6,35.9,33.05,32.99,28.6,21.5,20.8,20.4,18.0,14.9.

Example 36: Synthesis of phthalide

Other operations refer to Example 20, the raw material used is phthalic glycol (141.3 mg, 98% purity, 1.0 mmol), and the reaction time is 16 hours to obtain phthalide (88.3 mg, 66%) (petroleum ether: ethyl acetate = 15:1 to 10:1). ¹ H NMR (400MHz, CDCl ₃ ) δ7.92 (d, J=7.6Hz, 1H, Ar-H), 7.70 (td, J ₁ =7.6Hz, J ₂ =1.2Hz, 1H, Ar-H), 7.58-7.49 (m, 2H, Ar-H), 5.34 (s, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ171.1, 146.5, 134.0, 129.0, 125.62, 125.57, 122.1, 69.6.

Example 37: Synthesis of 7-octynoic acid

Under oxygen atmosphere (oxygen balloon), Fe(NO ₃ ) ₃ 9H ₂ O (202.8mg, 0.5mmol), TEMPO (78.3mg, 4.0mmol), NaCl (29.3mg, 0.5mmol), NaCl (29.3mg, 0.5mmol), 7-octyn-1-ol (631.4 mg, 5.0 mmol) and 1,2-dichloroethane (DCE, 20.0 mL). The reaction was stirred at room temperature for 20 hours, monitored by TLC (petroleum ether:ethyl acetate=5:1) until the reaction was complete. The reaction mixture was filtered through a short column of crude silica gel, rinsed with diethyl ether (3×40 mL). The solvent was spin-dried in vacuo, and the product 7-octynoic acid (599.1 mg, 85%) was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ HNMR (400MHz, CDCl ₃ ) δ11.29 (brs, 1H, COOH), 2.38 (t, J = 7.6Hz, 2H, CH ₂ ), 2.20 (td, J ₁ = 7.0Hz, J ₂ = 2.8Hz, 2H, C≡CCH ₂ ), 1.95 (t, J=2.8Hz, 1H, C≡CH), 1.71-1.61 (m, 2H, CH ₂ ), 1.60-1.41 (m, 4H, 2×CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.3, 84.2, 68.4, 33.9, 28.02, 27.99, 24.1, 18.2.

Example 38: Synthesis of Hexadecanoic Acid (Oxygen)

Under an oxygen atmosphere (oxygen balloon), add Fe(NO ₃ ) ₃ 9H ₂ O (1.6164g, 4.0mmol), TEMPO (625.3mg, 4.0mmol), KCl (298.4mg, 4.0mmol) into a 500mL three-necked flask in sequence and DCE (4.0 mL). Next, cetyl alcohol (9.8191 g, 98% purity, 40.0 mmol) was added. The reaction was stirred at room temperature for 16 hours, monitored by TLC (petroleum ether:ethyl acetate=5:1) until the reaction was complete. The reaction mixture was filtered through a short column of thick silica gel, and rinsed with diethyl ether (4×120mL). After the solvent was spin-dried in vacuo, the crude product was recrystallized and purified (the first recrystallization of petroleum ether: ethyl acetate = 10:1 gave 8.5404g of product, After the filtrate was spin-dried, petroleum ether:ethyl acetate=18:1 was recrystallized to obtain 1.1413g product) to obtain hexadecanoic acid (9.6817g, 94%). ¹ HNMR (400MHz, DMSO-d ₆ ) δ11.99 (brs, 1H, COOH), 2.18 (t, J=7.4Hz, 2H, CH ₂ ), 1.53-1.42 (m, 2H, CH ₂ ), 1.32- 1.16 (m, 24H, 12×CH ₂ ), 0.85 (t, J=6.6Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.8, 34.1, 31.9, 29.69, 29.67, 29.66, 29.59, 29.43, 29.37, 29.2, 29.0, 24.6, 22.7, 14.1.

Example 39: Synthesis of palmitic acid (air+oxygen)

Fe(NO ₃ ) ₃ 9H ₂ O (1.6162g, 4.0mmol), DCE (120mL), TEMPO (625.3mg, 4.0mmol), KCl (298.6mg, 4.0mmol) and ten Hexaalkyl alcohol (9.8968 g, 98% purity, 40.0 mmol). Then, the three-necked bottle is connected with a 70L air bag through an air extraction valve. After stirring at room temperature for 1.5 hours, the other port was connected to a 2L oxygen balloon through the exhaust valve as oxygen supplement. The reaction continued to stir at room temperature and was monitored by TLC (petroleum ether: ethyl acetate = 5:1) until the reaction was complete, a total of 21.5 hours. The reaction mixture was filtered through a short column of thick silica gel, rinsed with diethyl ether (4×120mL). After the solvent was spin-dried in vacuo, the crude product was recrystallized (petroleum ether:ethyl acetate=15:1) and purified to obtain palmitic acid (9.0540g ,88%). ¹ H NMR (400MHz, DMSO-d ₆ ) δ11.99 (brs, 1H, COOH), 2.18 (t, J=7.4Hz, 2H, CH ₂ ), 1.52-1.43 (m, 2H, CH ₂ ), 1.30 -1.19(m,24H,12×CH ₂ ),0.85(t,J=6.8Hz,3H,CH ₃ ); ¹³ CNMR(100MHz,CDCl ₃ )δ180.6,34.1,31.9,29.70,29.69,29.67, 29.66, 29.65, 29.59, 29.44, 29.37, 29.24, 29.1, 24.7, 22.7, 14.1.

Example 40: Synthesis of palmitic acid (slow air flow)

Add Fe(NO ₃ ) ₃ 9H ₂ O (9.6952g, 24.0mmol), TEMPO (3.7514g, 24.0mmol), KCl (1.7885g, 24.0mmol) and 1,2-dichloro Ethane (DCE, 400 mL). After stirring at room temperature for 10 minutes, cetyl alcohol (59.3883 g, 98% purity, 40.0 mmol) and DCE (100 mL) were added. The three-neck flask was fed with a slow air flow through the exhaust valve, and the reaction was stirred at room temperature, monitored by TLC (petroleum ether:ethyl acetate=5:1) until the reaction was complete after 24 hours. The reaction mixture was filtered through a short column of thick silica gel, rinsed with diethyl ether (3×500mL). After the solvent was spin-dried in vacuo, the crude product was recrystallized (petroleum ether:ethyl acetate=20:1) and purified to obtain palmitic acid (55.0232g ,89%). ¹ H NMR (400MHz, DMSO-d ₆ ) δ11.99 (brs, 1H, COOH), 2.18 (t, J=7.4Hz, 2H, CH ₂ ), 1.52-1.43 (m, 2H, CH ₂ ), 1.31 -1.18 (m, 24H, 12×CH ₂ ), 0.85 (t, J=6.6Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.5, 34.1, 31.9, 29.67, 29.65, 29.64 ,29.62,29.57,29.42,29.35,29.2,29.0,24.7,22.7,14.1.

Example 41: Synthesis of dodecanoic acid

Under an oxygen atmosphere (oxygen balloon), Fe(NO ₃ ) ₃ ·9H ₂ O (40.4mg, 0.10mmol), 2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO, 15.5mg, 0.10 mmol), KCl (7.5 mg, 0.10 mmol), dodecanal (184.3 mg, 1.0 mmol) and 1,2-dichloroethane (DCE, 4 mL) were added to a Schlenk tube. Stir at room temperature for 12 h, and monitor by TLC until the reaction is complete. The reaction mixture was filtered through a short column of crude silica gel, rinsed with diethyl ether (75 mL), and concentrated to obtain a crude product. The crude product was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the corresponding dodecanoic acid (187.9 mg, 94%). Melting point: 43-44°C (petroleum ether/ethyl acetate recrystallization) (literature value: 43-44°C); ¹ H NMR (400MHz, CDCl ₃ ) δ=11.56(brs,1H,COOH),2.35(t, J＝7.4Hz, 2H, CH ₂ ), 1.63(quint, J＝7.1Hz, 2H, CH ₂ ), 1.40-1.18(m, 16H, 8×CH ₂ ), 0.88(t, J＝6.6Hz, 3H , CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ180.6, 34.1, 31.9, 29.6, 29.4, 29.3, 29.2, 29.0, 24.7, 22.7, 14.1; MS (EI) m/z (%): 200 (M ⁺ ,20.99),73(100);IR(neat):v＝2954,2916,2871,2848,1697,1470,1429,1411,1351,1328,1302,1277,1248,1220,1193,1084cm ^-1 .

Example 42: Synthesis of cyclohexylcarboxylic acid

Other operations refer to Example 41, the raw material used is cyclohexanal, and the reaction time is 12 hours to obtain cyclohexylcarboxylic acid (115.4 mg, 90%) (petroleum ether: ethyl acetate = 5:1). ¹ H NMR (400MHz, CDCl ₃ ) δ=11.43(brs,1H,COOH),2.33(tt,J=11.2,3.6Hz,1H,H _a ),2.00-1.88(m,2H,H _b ),1.84 -1.70(m,2H,H _e ),1.70-1.58(m,1H,H _f ),1.55-1.38(m,2H,H _c ),1.37-1.18(m,3H,H _d and H _g ); ¹³ C NMR (100MHz, CDCl ₃ ) δ=182.9, 42.9, 28.7, 25.6, 25.3; MS (EI) m/z (%): 128 (M ⁺ ,53.29), 55 (100); IR (neat): v=2930,2855,1698,1451,1417,1311,1295,1256,1212,1182,1136,1021cm ^-1 .

Example 43: Synthesis of octanoic acid

Refer to Example 41 for other operations, the raw material used was octanal (128.1 mg), and the reaction time was 12 hours to obtain octanoic acid (138.4 mg, 96%) (petroleum ether: ethyl acetate = 5:1). ¹ H NMR (400MHz, CDCl ₃ ) δ11.33 (brs, 1H, COOH), 2.35 (t, J=7.4Hz, 2H, CH ₂ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.38-1.22 (m, 8H, 4×CH ₂ ), 0.88 (t, J=6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ=180.6, 34.1, 31.6, 29.0, 28.9, 24.6, 22.6, 14.0; MS (EI) m/z (%): 144 (M ⁺ , 2.09), 60 (100); IR (neat, cm ^-1 ) = 2956, 2925, 2857, 1706, 1459, 1412 ,1379,1275,1230,1203,1108cm ^-1 .

Example 44: Synthesis of Phenylpropionic Acid

Other operations refer to Example 41, the raw material used is phenylpropanal (141.3mg, 98% purity, 1.0mmol), and the reaction time is 12 hours to obtain phenylpropionic acid (144.9mg, 96%) (petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ )δ11.56(brs,1H,COOH),7.32-7.25(m,2H,Ar-H),7.23-7.16(m,2H,Ar-H),2.95(t, J=7.8Hz, 2H, CH ₂ ), 2.67 (t, J=7.8Hz, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ179.6, 140.1, 128.5, 128.2, 126.3, 35.6, 30.5; MS (EI) m/z (%): 150 (M ⁺ , 50.1), 91 (100); IR (neat, cm ^-1 ) 3030-2620, 1693, 1602, 1497, 1448, 1427, 1407, 1358, 1300 ,1216,1158,1082cm ^-1 .

Example 45: Synthesis of dodecanoic acid

Fe(NO ₃ ) ₃ 9H ₂ O (40.5 mg, 0.1 mmol) and DCE (4.0 mL) were added to a 100 mL round bottom flask, followed by TEMPO (15.6 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol) , dodecanal (183.8 mg, 1.0 mmol) and DCE (1.0 mL). The round bottom bottle is connected to an air balloon through a pumping valve. The reaction was stirred at room temperature for 16 hours until the reaction was completed as monitored by TLC (petroleum ether:ethyl acetate=5:1). The reaction mixture was filtered through a short column of crude silica gel and rinsed with diethyl ether (75mL). After the solvent was spin-dried in vacuo, silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) was purified to obtain dodecanoic acid (176.5mg, 88%) . ¹ H NMR (400MHz, CDCl ₃ ) δ11.49 (brs, 1H, COOH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 1.63 (quint, J=7.3Hz, 2H, CH ₂ ), 1.40-1.18 (m, 16H, 8×CH ₂ ), 0.88 (t, J=6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ=180.5, 34.1, 31.9, 29.6, 29.4, 29.3, 29.2, 29.0, 24.6, 22.7, 14.1.

Example 46: Synthesis of cyclohexylcarboxylic acid

Other operations refer to Example 45, the raw material used is cyclohexylformaldehyde (112.7mg, 1.0mmol), and the reaction time is 16 hours to obtain cyclohexylcarboxylic acid (106.4mg, 83%) (petroleum ether: ethyl acetate = 5:1) . ¹ H NMR (400MHz, CDCl ₃ ) δ=11.42(brs,1H,COOH),2.33(tt,J=11.2,3.6Hz,1H,H _a ),2.00-1.88(m,2H,H _b ),1.84 -1.70(m,2H,H _e ),1.70-1.60(m,1H,H _f ),1.55-1.38(m,2H,H _c ),1.37-1.18(m,3H,H _d and H _g ); ¹³ CNMR (100MHz, CDCl ₃ ) δ＝182.9, 42.9, 28.7, 25.6, 25.3.

Example 47: Synthesis of octanoic acid

Refer to Example 45 for other operations. The raw material used was octanal (128.7 mg, 1.0 mmol), and the reaction time was 16 hours to obtain octanoic acid (139.7 mg, 97%) (petroleum ether: ethyl acetate = 5:1). ¹ H NMR (400MHz, CDCl ₃ ) δ = 11.02 (brs, 1H, COOH), 2.35 (t, J = 7.6Hz, 2H, CH ₂ ), 1.63 (quint, J = 7.4Hz, 2H, CH ₂ ), 1.38-1.18 (m, 8H, 4×CH ₂ ), 0.88 (t, J=6.8Hz, 3H, CH ₃ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ=180.6, 34.1, 31.6, 29.0, 28.9, 24.6, 22.6, 14.0.

Example 48: Synthesis of Phenylpropionic Acid

Other operations refer to Example 45, the raw material used is phenylpropanal (141.5mg, 98% purity, 1.0mmol), and the reaction time is 16 hours to obtain phenylpropionic acid (147.7mg, 98%) (petroleum ether: ethyl acetate = 5:1 to 2:1). ¹ H NMR (400MHz, CDCl ₃ )δ11.09(brs,1H,COOH),7.32-7.25(m,2H,Ar-H),7.24-7.17(m,2H,Ar-H),2.95(t, J=7.8Hz, 2H, CH ₂ ), 2.67 (t, J=7.8Hz, 2H, CH ₂ ); ¹³ C NMR (100MHz, CDCl ₃ ) δ179.5, 140.1, 128.5, 128.2, 126.3, 35.6, 30.5.

Example 49: Synthesis of (Ra)-7,8-eicosenoic acid (natural product phlomic acid)

The synthesis of 7-octynoic acid refers to Example 30.

Synthesis of 7-octynoic acid methyl ester

Into a round bottom flask was added the substrate 7-octynoic acid (981.7 mg, 7.0 mmol) and Et ₂ O/MeOH mixed solvent (4/1, 35 mL). The system was lowered to 0°C, TMSCHN ₂ (2.0M, 5.25mL) was added dropwise, returned to room temperature naturally and stirred. TLC showed the reaction was complete after 2 hours. Spin off the solvent. Purification by silica gel column chromatography (petroleum ether/diethyl ether=30/1) gave 7-octynoic acid methyl ester (898.3 mg, 83%): ¹ H NMR (400MHz, CDCl ₃ ) δ3.67 (s, 3H, OMe) ,2.33(t,J=7.4Hz,2H,CH ₂ ),2.20(td,J ₁ =6.9Hz,J ₂ =2.5Hz,2H,≡CCH ₂ ),1.95(t,J=2.6Hz,1H, ≡CH),1.70-1.60(m,2H,CH ₂ ),1.60-1.50(m,2H,CH ₂ ),1.49-1.39(m,2H,CH ₂ ); ¹³ C NMR(100MHz,CDCl ₃ )δ174 .0, 84.2, 68.3, 51.4, 33.8, 28.1, 28.0, ^24.3 , 18.1; ,1174,1145,1087,1071,1008.MS(ESI)m/z(%):155.1(M+1) ^- .

Synthesis of (R _a )-7,8-eicosenoic acid methyl ester:

Under argon atmosphere, CuBr ₂ (134.1mg, 0.6mmol), (S)-dimethylprolinol (387.2mg, 3.0mmol), methyl 7-octynoate (694.2 mg, 4.5mmol)/dioxane (4.5mL) and dodecanal (830.1mg, 4.5mmol)/dioxane (4.5mL). Seal the sealed tube tightly with a polytetrafluoroethylene stopper and place it in a preheated 130°C oil bath Stir for 12 hours. TLC plate monitoring (petroleum ether/diethyl ether=5/1). The resulting mixture was diluted with 90 mL of _Et2O and washed with 60 mL of 3M hydrochloric acid solution. The layers were separated, and the aqueous phase was extracted with 30×3 mL Et ₂ O. The organic phases were combined, washed with saturated NaCl solution, and dried over anhydrous NaSO ₄ . After filtration and spin-drying, silica gel column chromatography (petroleum ether/diethyl ether=100/1) separated to obtain (R _a )-7,8-eicosenoic acid methyl ester (565.2 mg, 58%). 95%ee(HPLC conditions: Chiralcel PA-H column, hexane/i-PrOH=100/0, 1.0mL/min, λ=214nm, t _R (major)=17.2min, t _R (minor)=22.1min) ; [α] _D ^30.6 = -36.8 (c = 1.015, CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 5.11-5.00 (m, 2H, CH = C = CH), 3.66 (s, 3H, CH ₃ ), 2.30(t, J=7.6Hz, 2H, CH ₂ ), 2.02-1.93(m, 4H, 2×CH ₂ ), 1.63(quint, J=7.5Hz, 2H, CH ₂ ), 1.46- 1.20(m,22H,11×CH ₂ ),0.88(t,J=6.8Hz,3H,CH ₃ ); ¹³ CNMR(100MHz,CDCl ₃ )δ203.8,174.2,91.1,90.5,51.4,34.0,31.9,29.65 ,29.63,29.62,29.5,29.3,29.2,29.1,29.0,28.73,28.71,28.6,24.8,22.7,14.1; IR(neat)ν(cm ^-1 )2923,2853,1962,1742,1462,1437,1362 , 1255, 1199, 1170, 1087, 1012; MS (EI) m/z (%) 322 (M ⁺ ,6.73), 150 (100); HRMS calcd.for C ₂₁ H ₃₈ O ₂ (M ⁺ ): 322.2872 ;Found: 322.2876.

Synthesis of product (R _a )-7,8-eicosenoic acid (phlomic acid):

KOH (141.0 mg, 2.5 mmol), mixed solvent (5 mL, MeOH/H ₂ O = 4/1), and (R _a )-7,8-eicosenoic acid methyl ester ( 322.0 mg, 1 mmol)/mixed solvent (5 mL, MeOH/H ₂ O=4/1). The system was stirred at 60°C, monitored by TLC, and the reaction was complete after 2 hours. The system was placed in an ice bath, and 3M HCl (ca. 1 mL) was added dropwise. The MeOH was _swirled off and 30 mL of _CH2Cl2 and 25 mL of water were added. The liquid was separated, the organic phase was separated, and the aqueous phase was extracted with CH ₂ Cl ₂ (15 mL×3). The organic phases were combined, washed with saturated NaCl solution, and dried over anhydrous NaSO4. Filtration, spin-drying, and silica gel column chromatography (petroleum ether/diethyl ether=10/1 to 2/1) separated the natural product phlomic acid (283.6 mg, 92%). ¹ H NMR (400MHz, CDCl ₃ ) δ11.7 (brs, 1H, COOH), 5.11-5.01 (m, 2H, CH=C=CH), 2.35 (t, J=7.6Hz, 2H, CH ₂ ), 2.02-1.93(m, 4H, 2×CH ₂ ), 1.65(quint, J=7.5Hz, 2H, CH ₂ ), 1.49-1.20(m, 22H, 11×CH ₂ ), 0.88(t, J=6.8 Hz,3H,CH ₃ ); ¹³ CNMR(100MHz,CDCl ₃ )δ203.8,180.5,91.1,90.5,34.1,31.9,29.67,29.66,29.64,29.5,29.4,29.2,29.1,29.0,28.71,28.69,28.5, 24.5, 22.7, 14.1; IR (neat) ν (cm ^-1 ) 2915, 2849, 1964, 1708, 1683, 1458, 1415, 1331, 1285, 1246, 1200. MS (EI) m/z (%): 308 (M ⁺ ,5.91), 168(100); HRMS calcd. for C ₂₀ H ₃₆ O ₂ (M ⁺ ):308.2715; Found: 308.2717.

The ee value of the product (R _a )-7,8-eicosenoic acid (phlomic acid) was determined by methyl esterification derivation:

The natural product phlomic acid (55.9 mg, 0.2 mmol) and mixed solvent (5 mL, Et ₂ O/MeOH=4/1) were added to a round bottom flask. After the system was cooled to 0°C, 0.2 mL of TMSCHN ₂ (2M in hexane, 0.4 mmol) was added dropwise. The ice bath was removed, and the reaction mixture returned to room temperature naturally. The reaction was monitored by TLC, and the reaction was complete after 2.5 h. The solvent was spun off, and the liquid (R _a )-7,8-eicosenoic acid methyl ester (63.1 mg, 97%) was separated by silica gel column chromatography (petroleum ether/diethyl ether=100/1). 96%ee (HPLCconditions:Chiralcel PA-H column, hexane/i-PrOH=100/0, 1.0mL/min, λ=214nm, t _R (major)=23.7min, t _R (minor)=32.3min); [α] _D ^30.5 = -39.9 (c = 0.99, CHCl ₃ ); ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.11-5.01 (m, 2H, CH = C = CH), 3.67 (s, 3H, CH ₃ ), 2.36(t, J=7.6Hz, 2H, CH ₂ ), 2.03-1.92(m, 4H, 2×CH ₂ ), 1.63(quint, J=7.5Hz, 2H, CH ₂ ), 1.46-1.20 (m,22H,11×CH ₂ ),0.88(t,J=6.8Hz,3H,CH ₃ ); ¹³ C NMR (100MHz,CDCl ₃ )δ203.8,174.2,91.1,90.6,51.4,34.0,31.9,29.66 ,29.63,29.5,29.3,29.2,29.1,29.0,28.73,28.71,28.6,24.8,22.7,14.1.

Example 50: Synthesis of Dodecanoic Acid (Dodecanoic Acid)

Under an oxygen atmosphere (oxygen balloon), Fe(NO ₃ ) ₃ 9H ₂ O (40.7mg, 0.10mmol), dodecanal (184.2mg, 1.0mmol) and 1,2-dichloroethane (DCE, 4 mL) into the Schlenk tube. Stir at room temperature for 12 h, and monitor by TLC until the reaction is complete. The reaction mixture was filtered through a short column of crude silica gel, rinsed with diethyl ether (75 mL), and concentrated to obtain a crude product. 35 μL of dibromomethane was added as an internal standard, and the yield of dodecanoic acid was 78% and that of dodecanoic acid was 11% as measured by quantitative hydrogen nuclear magnetic spectrum ( ¹ H NMR). The crude product was subjected to silica gel column chromatography (petroleum ether:ethyl acetate=20:1 to 5:1) to obtain dodecanoic acid and dodecanoic acid. Dodecanoic acid: ¹ H NMR (400MHz, CDCl ₃ ) δ11.49 (brs, 1H, COOH), 2.35 (t, J = 7.6Hz, 2H, CH ₂ ), 1.63 (quint, J = 7.2Hz, 2H, CH ₂ ), 1.38-1.21(m, 16H, 8×CH ₂ ), 0.88(t, J=6.6Hz, 3H, CH ₃ ); ¹³ CNMR(100MHz, CDCl ₃ )δ=180.6, 34.1, 31.9, 29.6 , 29.4, 29.3, 29.2, 29.0, 24.6, 22.7, 14.1. Dodecanoic acid: ¹ HNMR (400MHz, CDCl ₃ ) δ11.38 (brs, 1H, CO ₃ H), 2.42 (t, J＝7.6Hz ,2H,CH ₂ ), 1.70(quint,J=7.3Hz,2H,CH ₂ ),1.39-1.19(m,16H,8×CH ₂ ),0.88(t,J=6.8Hz,3H,CH ₃ ) ; ¹³ CNMR (100MHz, CDCl ₃ ) δ=174.7, 31.9, 30.4, 29.54, 29.51, 29.32, 29.29, 29.0, 28.9, 24.6, 22.7, 14.1.

Claims (14)

1. A method for oxidizing alcohol or aldehyde by oxygen is characterized in that at room temperature, in an organic solvent, oxygen is used as an oxidizing agent, alcohol, diol or aldehyde is used as a raw material, ferric nitrate, 2,6, 6-tetramethylpiperidine oxynitride and inorganic halide are used as catalysts, the reaction is carried out under neutral conditions, the alcohol or aldehyde is oxidized to generate acid, and the diol is oxidized to generate lactone or diacid; wherein,

the starting alcohol is R₁CH₂OH；R₁Comprises a carbon chain of C1-C16, a carbocyclic or heterocyclic ring of C3-C8, and a fluorine-, chlorine-, bromine-, iodine-, aryl-, hetero-ringThe structure of ring, ester group, ether bond, alkynyl, alkyl, terpenoid and steroid of double bond functional group;

the raw material diols include 1, 4-diol, 1, 5-diol and 1, 8-diol;

the starting aldehyde is R₂CHO；R₂Comprises C1-C16 carbon chain, C3-C8 carbocycle or heterocycle, and alkyl, terpenoid and steroid structure containing fluorine, chlorine, bromine, iodine, aryl, heterocycle, ester group, ether bond, alkynyl and double bond functional group.

2. A method for oxidizing alcohol or aldehyde by oxygen is characterized in that at room temperature, in an organic solvent, oxygen is used as an oxidizing agent, aldehyde is used as a raw material, ferric nitrate is used as a catalyst, and the aldehyde is oxidized to generate acid and peroxy acid under a neutral condition;

wherein the starting aldehyde is R₂CHO；R₂Comprises C1-C16 carbon chain, C3-C8 carbocycle or heterocycle, and alkyl, terpenoid and steroid structure containing fluorine, chlorine, bromine, iodine, aryl, heterocycle, ester group, ether bond, alkynyl and double bond functional group.

3. The method for the oxygen oxidation of an alcohol or aldehyde according to claim 1 or 2, wherein the aryl group is a phenyl group, an alkoxyphenyl group, a nitrophenyl group, a halophenyl group, a thienyl group, a furyl group, or a naphthyl group; the alkoxy phenyl is methoxyphenyl and ethoxyphenyl, and the halogenated phenyl is fluorophenyl, chlorophenyl, bromophenyl and iodophenyl;

the heterocyclic ring is furan ring or thiophene ring.

4. The method for oxidizing alcohol or aldehyde with oxygen according to claim 2, wherein the molar ratio of the raw material aldehyde to the raw material ferric nitrate is 100 to 10: 1.

5. The method for oxidizing alcohol or aldehyde with oxygen according to claim 1, wherein the molar ratio of the raw material, ferric nitrate, 2,6, 6-tetramethylpiperidine nitroxide, and inorganic halide is 100:1 to 10:1 to 20:1 to 10.

6. The method for oxidizing an alcohol or aldehyde with oxygen according to claim 5, wherein the molar ratio of the raw material, ferric nitrate, 2,6, 6-tetramethylpiperidine nitroxide, inorganic halide is 100:10:20: 10.

7. The method for the oxygen oxidation of an alcohol or aldehyde according to claim 1, wherein the inorganic halide is a lithium halide, a sodium halide, a potassium halide, a rubidium halide, a cesium halide, and the halogen atom is fluorine, chlorine, bromine, or iodine.

8. The method for the oxygen oxidation of an alcohol or aldehyde according to claim 7, wherein the inorganic halide is potassium chloride or sodium chloride.

9. The method for oxygen oxidizing an alcohol or aldehyde according to claim 1, wherein the reaction time is 1 to 48 hours.

10. The method for oxidizing an alcohol or aldehyde with oxygen according to claim 1, wherein the oxygen is pure oxygen or oxygen in air.

11. The method for oxygen oxidizing an alcohol or aldehyde according to claim 1, wherein the neutral condition is that no protic acid or base is added.

12. The method for the oxygen oxidation of an alcohol or aldehyde according to claim 1, wherein the organic solvent is one or more selected from the group consisting of ethyl acetate, dichloromethane, 1, 2-dichloroethane, 1-dichloroethane, 1, 2-dichloropropane, 1, 3-dichloropropane, nitromethane, ethylene glycol dimethyl ether, dioxane, tetrahydrofuran, acetonitrile, benzene, and toluene.

13. The method for oxidizing an alcohol or aldehyde with oxygen according to claim 1 or 2, wherein the oxygen may be oxygen in air;

wherein, the method adopted when introducing air is to take an air bag as a main source of oxygen, and an oxygen ball is added as supplement after reacting for 1.5 hours; or by a slow air flow method, allowing air to flow slowly through the reaction vessel.

14. Synthesis of (R)_a) A method of producing (R) -7, 8-eicosenoic acid, wherein said (R) is_a) The structure of the-7, 8-eicosenoic acid is shown in the formula (I), and the method comprises the following steps:

(1) taking 7-octyne-1-ol as a raw material, taking ferric nitrate, 2,6, 6-tetramethylpiperidine oxynitride and inorganic halide as catalysts, and carrying out oxidation reaction to obtain 7-octynoic acid;

(2) carrying out methylation reaction on the 7-octynoic acid prepared in the step (1) to obtain 7-octynoic acid methyl ester;

(3) catalyzing the 7-octynoic acid methyl ester prepared in the step (2) by copper bromide and dimethyl prolinol to perform EATA reaction to obtain dienoic acid methyl ester;

(4) hydrolyzing the methyl dienoate prepared in step (3) in a methanol/water system in the presence of potassium hydroxide to obtain the axial chiral dienoic acid (R)_a) -7, 8-eicosenoic acid;