Naphthalene ring carbon-14 labeled 2, 6-diisopropyl naphthalene and synthesis method thereof

Abstract

The scheme provides naphthalene ring carbon-14 labeled 2, 6-diisopropyl naphthalene and a synthesis method thereof, and the synthesis method comprises the following steps: S1, synthesizing 1-{2-[(1-14C) cyanomethyl]-3-methylbutyl}-4-isopropyl benzene; s2, synthesizing 3-[(4-isopropyl phenyl) methyl]-4-methyl [1-14C] ethyl valerate; s3, synthesizing 3-[(4-isopropyl phenyl) methyl]-4-methyl [1-14C] valeric acid; s4, synthesizing 3, 7-diisopropyl-[1-14C]-tetrahydronaphthalene ketone; and S4, synthesizing 3, 7-diisopropyl-[1-14C]- S5, synthesizing 3, 7-diisopropyl-[1-14C]-tetrahydronaphthalene alcohol; S6, synthesizing 3, 7-diisopropyl-[1-14C]-3, 4-2H-naphthalenone; S5, synthesizing 3, 7-diisopropyl-[1-14C]-tetrahydronaphthalene alcohol; s7, 14C-2, 6-diisopropyl naphthalene is synthesized, the synthesized 14C-2, 6-diisopropyl naphthalene takes a naphthalene ring as a marking position, and the 14C-2, 6-diisopropyl naphthalene can serve as a tracer agent to be used for tracing of insecticides in plants, soil and water bodies and research on other aspects.

Description

Technical Field

[0001] The invention belongs to the field of radiochemistry, and particularly relates to naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene and a synthesis method thereof. Background Art

[0002] As a crucial organic chemical raw material, 2,6-diisopropylnaphthalene holds a significant position in the chemical industry. Furthermore, its biological activity offers potential applications in environmentally friendly insecticides, plant growth regulators, and preservatives for stored vegetables, making it increasingly important in the pesticide field.

[0003] However, current research on 2,6-diisopropylnaphthalene faces numerous limitations. Studies of its behavior in plants are limited to the detection of the parent compound using chromatography or chromatography-mass spectrometry, with a significant lack of research on its metabolism and degradation products. This situation directly results in a superficial understanding of its metabolic processes and environmental behavior, hindering a deeper understanding of its transformation and impact mechanisms within ecosystems.

[0004] In the international development of new pesticides, radioactive isotope tracing technology is indispensable for new drug research. Regarding 2,6-diisopropylnaphthalene, its chemical transformation in complex environments and within organisms remains unclear from a chemical stability perspective. Carbon-14 labeling helps accurately track its structural changes. Regarding metabolic stability, due to a lack of research on metabolism and degradation products, it is impossible to accurately assess its persistence and transformation characteristics within organisms. Radioactive labeling can provide direct evidence. From a toxicological perspective, in-depth exploration of its metabolic pathways and mechanisms of action is key to assessing its impact on the ecological environment and biosafety. Carbon-14 labeling of 2,6-diisopropylnaphthalene is essential for conducting these studies.

[0005] Therefore, there is an urgent need to conduct research on carbon-14 labeled 2,6-diisopropylnaphthalene to fill the existing research gaps and promote the comprehensive understanding and rational application of this compound. Summary of the Invention

[0006] The purpose of the present invention is to provide a naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene and a synthesis method thereof. The naphthalene ring is used as the labeling position to successfully synthesize the naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene. The naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene can be used as a tracer for the tracing of pesticides in plants, soil and water bodies and other research, so as to solve the problems of the lack of effective radioactive tracers in existing research and insufficient research on its metabolic process and environmental behavior.

[0007] To achieve the above objectives, in a first aspect, the present technical solution provides a method for synthesizing 2,6-diisopropylnaphthalene labeled with 14 carbon atoms of a naphthalene ring, comprising the following steps: S1: Synthesis of 1-{2-[(1- 14 C) cyanomethyl]-3-methylbutyl}-4-isopropylbenzene; Under the protection of inert gas, 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene was reacted with 14 C-sodium cyanide was dissolved in an aprotic solvent and an inorganic base was added to stir the reaction. After the reaction, the organic phases were extracted and combined. The organic phases were washed, dried, filtered and concentrated, and then rapidly purified by column chromatography to obtain 1-{2-[(1- 14 C) cyanomethyl]-3-methylbutyl}-4-isopropylbenzene; S2: Synthesis of 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate; Under the protection of inert gas, 1-{2-[(1- 14 C) Dissolve [methyl]-3-methylbutyl]-4-isopropylbenzene in an alcohol solvent and add an acid solvent to stir the reaction. After the reaction is completed, concentrate to dryness and flash column chromatography to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate; S3: Synthesis of 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]valeric acid; Under the protection of inert gas, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate was dissolved in a polar solvent and an inorganic base was added and stirred for reaction. After the reaction, dilute hydrochloric acid was added and extracted and backwashed. The mixture was dried, filtered and concentrated to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]valeric acid; S4: Synthesis of 3,7-diisopropyl-[1- 14 C]-tetralone; Under the protection of inert gas, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] valeric acid was dissolved in an acid solution and dehydrated, stirred and reacted at high temperature, and after the reaction was completed, the organic phases were extracted and combined, washed with an alkaline solution and saturated brine, dried, filtered and concentrated, and then subjected to rapid column chromatography to obtain 3,7-diisopropyl-[1- 14 C]-tetralone; S5: Synthesis of 3,7-diisopropyl-[1- 14 C]-Tetrahydronaphthol: Under the protection of inert gas, 3,7-diisopropyl-[1- 14C]-tetralone was dissolved in an aprotic solvent and a reducing agent was added, and the reaction was stirred at low temperature. After the reaction was completed, the mixture was quenched with water and acid was added to adjust the acidity, and then extracted. The organic phases were combined and washed with saturated brine, dried, filtered, concentrated, and then rapidly chromatographed to obtain 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol; S6: Synthesis of 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone; Under the protection of inert gas, 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol was dissolved in an aprotic solvent, an acid solution was added to catalyze and dehydrate, and the reaction was stirred at a high temperature. After the reaction was completed, the organic phases were extracted and combined, and the organic phases were washed, dried, filtered and concentrated, and then subjected to rapid column chromatography to obtain 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone; S7: Synthesis 14 C-2,6-diisopropylnaphthalene: Under the protection of inert gas, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone is dissolved in an aprotic solvent, an oxidant is added for oxidation, and the reaction is stirred at a high temperature. After the reaction is completed, the organic phases are combined, washed, dried, filtered, concentrated, and then rapidly column chromatographed to obtain 14 C-2,6-diisopropylnaphthalene.

[0008] This program will 14 C-sodium cyanide is substituted with self-made iodinated aromatic hydrocarbon to obtain 14 The C-cyano substituent is reacted with thionyl chloride methanol to form an ester, which is then hydrolyzed to obtain a carboxylic acid, which is then cyclized to form a naphthone under the action of PPA, which is then reduced with LAH and then eliminated to obtain a crude product. The crude product is purified by preparative HPLC to obtain the target product of the present invention, naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene. The specific activity of the labeled substance of this scheme is in the range of 1.0 to 300 mCi / mmol; the chemical purity and radiochemical purity are both greater than 98%, and the synthesized 14 C-2,6-diisopropylnaphthalene uses the naphthalene ring as the labeling position and can be used as a tracer for the tracing of pesticides in plants, soil and water and other research.

[0009] In step S1, 14 C-Sodium cyanide dissociates in alkaline environment 14 C-cyanide ion, 4C-cyanide ion acts as a nucleophile to attack the carbon atom with a leaving group on 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene, thereby undergoing a nucleophilic substitution reaction. The leaving group leaves 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene with a pair of electrons to generate 14 C-cyano substituent: 1-{2-[(1- 14 C) Cyanomethyl]-3-methylbutyl}-4-isopropylbenzene.

[0010] In addition, in step S1, the aprotic solvent is selected from one or any combination of DMSO, DMF, and THF. Preferably, the aprotic solvent is selected from DMSO.

[0011] In step S1, the inorganic base is selected from one or any combination of LiOH, NaOH, and KOH. Preferably, the inorganic base is NaOH.

[0012] In step S1, 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene is reacted with 14 C-sodium cyanide was dissolved in an aprotic solvent and an inorganic base was added and stirred, and the mixture was placed at 0-25°C and stirred for 2-12 hours. After the reaction was completed, water and ethyl acetate were added for extraction. The organic phases were combined, washed with saturated brine, dried, filtered, concentrated, and flash column chromatography was performed to obtain 1-{2-[(1- 14 C) Cyanomethyl]-3-methylbutyl}-4-isopropylbenzene.

[0013] In some specific embodiments, the reaction equation of step S1 is as follows: .

[0014] The chemical formula of 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene involved in step S1 is shown in the following formula (II): .

[0015] Regarding the 1-{2-[(1- 14 C) The chemical formula of cyanomethyl]-3-methylbutyl}-4-isopropylbenzene is shown in the following formula (III): .

[0016] In step S2, an acid solvent and an alcohol solvent undergo a nucleophilic addition reaction to obtain an active intermediate, which reacts with 1-{2-[(1- 14 C) Cyanomethyl]-3-methylbutyl}-4-isopropylbenzene undergoes a nucleophilic substitution reaction, thereby causing 1-{2-[(1- 14 C) Cyanomethyl]-3-methylbutyl}-4-isopropylbenzene 14The carbon atom adjacent to the C-cyano group is attracted by the active intermediate and undergoes a nucleophilic attack to form an ester bond, generating 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate.

[0017] In step S2, the alcohol solvent is selected from one or any combination of MeOH, EtOH, and n-BuOH. Preferably, the alcohol solvent is selected from EtOH.

[0018] In step S2, the acid solvent is selected from one or any combination of SOCl2, H2SO4, and HCl. Preferably, the acid solvent is selected from SOCl2.

[0019] In step S2, 1-{2-[(1- 14 C) Dissolve [methyl]-3-methylbutyl]-4-isopropylbenzene in an alcohol solvent and add an acid solvent to stir the reaction. Stir the reaction at 0-80°C for 1-12 hours. After the reaction is completed, concentrate to dryness and flash column chromatography to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate.

[0020] In a specific embodiment, the reaction equation involved in step S2 is as follows: .

[0021] Regarding the 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] The structural formula of ethyl valerate is shown in the following formula (IV): .

[0022] In step S3, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] Ethyl valerate undergoes hydrolysis in a polar solvent under the action of an inorganic base to form a carboxylate, which is then acidified and converted into a carboxylic acid under the action of dilute hydrochloric acid to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] valeric acid.

[0023] In step S3, the polar solvent is selected from one or any combination of MeOH, EtOH, H2O, THF, and dioxane. Preferably, the polar solvent is selected from EtOH and H2O.

[0024] In step S3, the inorganic base is selected from one or any combination of LiOH, NaOH, and KOH. Preferably, the inorganic base is selected from KOH.

[0025] In step S3, 3-[(4-isopropylphenyl)methyl]-4-methyl[1-14 C] ethyl valerate was dissolved in a polar solvent and an inorganic base was added, and the mixture was stirred at 0-80°C for 2-12 hours. After the reaction was completed, dilute hydrochloric acid was added to adjust the acidity, and the mixture was extracted twice with DCM and backwashed once with saturated brine, dried, filtered and concentrated to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] valeric acid.

[0026] In one embodiment, the reaction equation involved in step S3 is as follows: .

[0027] Regarding the 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 The chemical formula of valeric acid is shown in the following formula (V): .

[0028] In step S4, under the catalytic action of the acid solution, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] Valeric acid undergoes an intramolecular dehydration reaction, in which the acid provides a proton to protonate the oxygen atom on the carboxyl group, and an electrophilic substitution reaction occurs within the molecule. As the carboxyl group leaves, a new carbon-carbon bond is formed with the carbon atom at the adjacent position on the benzene ring, forming product V1 containing a naphthalene ring structure.

[0029] In step S4, the acid solution is selected from one or any combination of H2SO4, PPA, and TsOH. Preferably, the acid solution is selected from PPA.

[0030] In step S4, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] valeric acid was dissolved in an acid solution and dehydrated, stirred at 50-120°C for 2-12 hours, and after the reaction was completed, water and ethyl acetate were added to the reaction system for extraction, the organic phases were combined, washed with 20% NaOH solution and saturated brine, dried, filtered, concentrated, and subjected to flash column chromatography to obtain the product 3,7-diisopropyl-[1- 14 C]-tetralone.

[0031] In one embodiment, the reaction equation of step S4 is as follows: .

[0032] Regarding the 3,7-diisopropyl-[1- 14 The chemical formula of [C]-tetralone is shown in the following formula (VI): .

[0033] In step S5, 3,7-diisopropyl-[1- 14 The carbonyl group in tetralone undergoes carbonyl reduction reaction with a reducing agent in an aprotic solvent, opening the carbonyl double bond, and the oxygen atom accepts an electron pair to form an oxygen anion, which is then protonated to obtain a hydroxyl group, thereby reducing the carbonyl group to a hydroxyl group to generate 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol.

[0034] In step S5, the aprotic solvent is selected from one or any combination of Et2O, THF, and 2-Me-THF. Preferably, the aprotic solvent is selected from THF.

[0035] In step S5, the reducing agent is selected from one or any combination of LiBHEt3, NaBH4, and LiAlH4. Preferably, the reducing agent is selected from LiAlH4.

[0036] In step S5, 3,7-diisopropyl-[1- 14 C]-tetralone was dissolved in an aprotic solvent and a reducing agent was added. The reaction was stirred at -10~30℃ for 1~12h. After the reaction was completed, the mixture was quenched with water and the acid was adjusted with dilute hydrochloric acid. The mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated brine, dried, filtered, concentrated, and then rapidly purified by column chromatography to obtain 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol.

[0037] In one embodiment, the reaction equation of step S5 is as follows: .

[0038] Regarding the 3,7-diisopropyl-[1- 14 The chemical formula of [C]-tetrahydronaphthol is shown in formula (VII): .

[0039] In step S6, 3,7-diisopropyl-[1- 14 The hydroxyl group in the tetrahydronaphthol undergoes an intramolecular dehydration elimination reaction under the catalysis of acid. The hydrogen atoms on the adjacent carbon atoms are removed in the form of protons under the catalysis of acid. At the same time, the carbon-oxygen bond is broken, and a double bond is formed between the two adjacent carbon atoms to generate a product containing an unsaturated bond, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone.

[0040] In step S6, the aprotic solvent is selected from one or any combination of Toluene, THF, and 2-Me-THF. Preferably, the aprotic solvent is selected from Toluene.

[0041] In step S6, the acid solution is selected from one or any combination of H2SO4, PPA, and TsOH. Preferably, the acid solution is selected from TsOH.

[0042] In step S6, 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol was dissolved in an aprotic solvent, and an acid solution was added to catalyze and dehydrate the mixture. The mixture was stirred at 50-120°C for 1-12 hours. After the reaction, water and ethyl acetate were added to the reaction system for extraction. The organic phases were combined and washed with saturated brine, dried, filtered, concentrated, and then rapidly chromatographed to obtain 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone.

[0043] In one embodiment, the reaction equation of step S6 is as follows: .

[0044] Regarding the 3,7-diisopropyl-[1- 14 The chemical formula of [C]-3,4-2H-naphthone is shown in the following formula (VIII): .

[0045] In step S7, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthalenone is oxidized by an oxidizing agent to obtain 3,7-diisopropyl-[1- 14 The electrons in C]-3,4-2H-naphthone cause the partial structure of the indene ring to undergo oxidation transformation to form a naphthalene ring structure, generating 14 C-2,6-diisopropylnaphthalene.

[0046] In step S7, the aprotic solvent is selected from one or any combination of Toluene, Benzene, and DCE. Preferably, the aprotic solvent is selected from Benzene.

[0047] In step S7, the oxidant is selected from one or any combination of anthraquinone-2-sulfonate sodium, chloranil, and 4-phenylpyridine-N-oxide. Preferably, the oxidant is selected from chloranil.

[0048] In step S7, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone was dissolved in an aprotic solvent, an oxidant was added for oxidation, and the reaction was stirred at 60-120°C for 2-12 hours. After the reaction, water and ethyl acetate were added to the reaction system for extraction, and the organic phases were combined. The organic phases were washed with saturated brine, dried, filtered, concentrated, and then rapidly chromatographed to obtain 14 C-2,6-diisopropylnaphthalene.

[0049] In one embodiment, the reaction equation of step S7 is as follows: .

[0050] Regarding the step S7 14 C-2,6-diisopropylnaphthalene is represented by the following formula (I): .

[0051] In a second aspect, this solution provides a naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene, which is synthesized according to the above-mentioned naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene synthesis method, and the chemical formula is shown in the following formula (I): .

[0052] The naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene synthesized in this protocol uses the naphthalene ring as the labeling position. The specific activity of the labeled product ranges from 1.0 to 300 mCi / mmol; both the chemical and radiochemical purities are greater than 98%.

[0053] Compared with the existing technology, this technical solution has the following characteristics and beneficial effects: This protocol successfully synthesized 2,6-diisopropylnaphthalene labeled with carbon-14 on the naphthalene ring, filling a gap in related research on radioactive tracers. It can be used for tracing pesticides in plants, soil, and water, as well as other research, to facilitate in-depth exploration of their metabolic processes and environmental behaviors. The specific activity range is 1.0–300 mCi / mmol, and both chemical and radiochemical purities are greater than 98%. The label is firm and not easily detached, meeting the requirements of biological and environmental tracing experiments and ensuring the accuracy and reliability of experimental results. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 This is the synthetic route for the carbon-14 labeling of 2,6-diisopropylnaphthalene in the present invention, wherein the asterisk indicates the carbon-14 labeling site.

[0055] Figure 2 This is the H NMR spectrum of 2,6-diisopropylnaphthalene labeled with carbon-14 of the naphthalene ring in the present invention.

[0056] Figure 3 It is a high performance liquid chromatogram of 2,6-diisopropylnaphthalene labeled with carbon-14 of the naphthalene ring in the present invention.

[0057] Figure 4 This is a GC-MS chart of 2,6-diisopropylnaphthalene labeled with carbon-14 of the naphthalene ring in the present invention.

[0058] Figure 5 This is the H NMR spectrum of the radioactive intermediate (VIII) in the present invention.

[0059] Figure 6 This is the H NMR spectrum of the radioactive intermediate (VII) in the present invention.

[0060] Figure 7 It is the nuclear magnetic resonance hydrogen spectrum of the radioactive intermediate (VI) in the present invention.

[0061] Figure 8 This is the H NMR spectrum of the radioactive intermediate (V) in the present invention.

[0062] Figure 9 This is the H NMR spectrum of the radioactive intermediate (III) in the present invention. DETAILED DESCRIPTION

[0063] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field are within the scope of protection of the present invention.

[0064] The following examples illustrate the present invention. The examples are only used to further illustrate the present invention and do not represent the scope of protection of the present invention. Non-essential modifications and adjustments made by others based on the present invention still fall within the scope of protection of the present invention.

[0065] S1: Under nitrogen atmosphere, 14 C-sodium cyanide (196.0 mg, 4 mmol, 55 mCi / mmol) was dissolved in anhydrous DMSO (14 mL), and NaOH (176.4 mg, 4.4 mmol) was added. The substrate 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene (1.4432 g, 4.4 mmol) was added and stirred vigorously at 25 °C for 12 h. After the reaction, water (20 mL) and ethyl acetate (15 mL x 3) were added to the reaction system for extraction. The organic phases were combined, washed with saturated brine (8 mL x 2), dried over anhydrous sodium sulfate, filtered, concentrated, and flash column chromatography with PE / EA = 40:1~20:1 to obtain a light yellow oily product 1-{2-[(1- 14 C) [Cyanomethyl]-3-methylbutyl]-4-isopropylbenzene (670.6 mg, 2.90 mmol, 72% yield): 1H NMR (400 MHz, Chloroform-d) δ7.19 (d, J = 7.7 Hz, 2H), 7.12 (d, J = 7.7 Hz, 2H), 2.90 (dt, J = 13.7, 5.5Hz, 2H), 2.48 (dd, J = 13.8, 9.9 Hz, 1H), 2.26 (qd, J = 17.0, 5.8 Hz, 2H), 1.93 (h, J = 6.6 Hz, 1H), 1.82 (dp, J = 11.2, 5.7 Hz, 1H), 1.27 (d, J = 7.1Hz, 6H), 1.05 (d, J = 6.8 Hz, 6H).

[0066] .

[0067] S2: Under nitrogen atmosphere, the product 1-{2-[(1- 14 C) Dissolve cyanomethyl]-3-methylbutyl}-4-isopropylbenzene (670.6 mg, 2.90 mmol) in EtOH (10 mL), add SOCl2 (1.7250 g, 14.5 mmol) dropwise at 0-5 °C, then heat to 78 °C and stir for 12 h. After the reaction, the reaction solution is concentrated to dryness and flash column chromatography PE / EA = 20:1-10:1 to obtain a light yellow oily product 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] Ethyl valerate (589.4 mg, 2.12 mmol, 73% yield): .

[0068] S3: The product obtained in the previous step, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] Ethyl valerate (589.4 mg, 2.12 mmol) was dissolved in EtOH (4 mL), and a solution of KOH (594.8 mg, 10.6 mmol) in water (4 mL) was added. The temperature was raised to 80 °C and stirred for 12 h. After the reaction, dilute hydrochloric acid (2 N) was added to the reaction solution to adjust the pH to 3-4, and then the solution was extracted with DCM (12 mL x 5), backwashed once with saturated brine (5 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a yellow solid 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]Valeric acid (487.5 mg, 1.95 mmol, 92% yield): 1H NMR (400 MHz, DMSO-d6) δ 12.05 (s, 1H), 7.15 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 2.84 (p, J = 6.9 Hz, 1H), 2.60 – 2.53 (m, 1H), 2.43 – 2.32 (m, 1H), 2.25 –2.13 (m, 1H), 2.05 – 1.90 (m, 2H), 1.73 – 1.56 (m, 1H), 1.19 (d, J = 6.9 Hz,6H), 0.86 (dd, J = 11.0, 6.8 Hz, 6H).

[0069] .

[0070] S4: Under nitrogen atmosphere, the product obtained in the previous step, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]valeric acid (487.5 mg, 1.95 mmol) was added to PPA (10 mL), and then the temperature was raised to 100 °C and stirred for 3 h. After the reaction was completed, water (15 mL) and ethyl acetate (10 mL x 3) were added to the reaction system for extraction. The organic phases were combined, washed with 20% NaOH solution (15 mL x 2) and saturated brine (15 mL x 1), dried over anhydrous sodium sulfate, filtered, concentrated, and flash column chromatography with PE / EA = 15:1~10:1 to obtain a light yellow oily product 3,7-diisopropyl-[1- 14 C]-Tetralone (320.1 mg, 1.38 mmol, 71% yield): 1 H NMR(400 MHz, Chloroform-d) δ 7.91 (d, J = 2.0 Hz, 1H), 7.38 (dd, J = 7.9, 2.1Hz, 1H), 7.22 (d, J = 7.9 Hz, 1H), 3.09 – 2.87 (m, 2H), 2.84 – 2.66 (m, 2H), 2.36 (dd, J = 16.5, 12.9 Hz, 1H), 2.00 (dddt, J = 13.1, 11.3, 6.1, 3.7 Hz, 1H), 1.77 – 1.67 (m, 1H), 1.27 (d, J = 6.9 Hz, 7H), 1.01 (dd, J = 6.8, 2.6Hz, 6H). .

[0071] S5: Under nitrogen atmosphere, the product obtained in the previous step, 3,7-diisopropyl-[1- 14 C]-tetralone (320.1 mg, 1.38 mmol) was dissolved in THF (5 mL), and LiAlH4 (1.2 mL, 1.2 mmol, 1.0 M in THF) was added dropwise at 0-5 °C, and then the temperature was raised to 25 °C and stirred for 2 h. After the reaction was completed, the mixture was quenched with water (10 mL), and the pH was adjusted to 5-6 with dilute hydrochloric acid (2 N). The mixture was extracted with ethyl acetate (10 mL x 5), and the organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a light yellow oily product 3,7-diisopropyl-[1- 14 C]-Tetrahydronaphthol (320.6 mg, 1.37 mmol, 99% yield): 1 H NMR (400 MHz, Chloroform-d) δ 7.49 (d, J = 1.8 Hz, 1H), 7.19 – 7.00 (m, 2H), 4.83 (dd, J = 10.9, 5.8 Hz, 1H), 2.93 (p, J = 6.9 Hz, 1H), 2.78 (ddd, J = 16.3,4.6, 2.0 Hz, 1H), 2.57 (dd, J = 16.3, 11.2 Hz, 1H), 2.31 (ddt, J = 11.9, 5.8,2.0 Hz, 1H), 1.78 (s, 1H), 1.64 (dtt, J = 17.2, 8.2, 3.1 Hz, 2H), 1.42 – 1.34(m, 1H), 1.28 (d, J = 6.9 Hz, 7H), 1.00 (td, J = 7.2, 6.5, 3.1 Hz, 6H). .

[0072] S6: Under nitrogen atmosphere, the product obtained in the previous step, 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol (320.6 mg, 1.37 mmol) was dissolved in Toluene (6 mL), TsOH (260.0 mg, 1.51 mmol) was added, and the temperature was raised to 110 °C and stirred for 12 h. After the reaction was completed, water (10 mL) and ethyl acetate (10 mLx3) were added to the reaction system for extraction. The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and flash column chromatography with PE / EA = 20:1~10:1 was used to obtain a light yellow oily product 3,7-diisopropyl-[1-14 C]-3,4-2H-naphthone (248.4 mg, 1.15 mmol, 84% yield): 1 H NMR(400 MHz, Chloroform-d) δ 7.11 – 6.96 (m, 2H), 6.92 (d, J = 1.9 Hz, 1H), 6.47(dd, J = 9.7, 2.3 Hz, 1H), 5.96 (dd, J = 9.7, 3.4 Hz, 1H), 2.88 (hept, J =7.0 Hz, 1H), 2.83 – 2.64 (m, 2H), 2.40 – 2.22 (m, 1H), 1.75 (hept, J = 6.7Hz, 1H), 1.27 (d, J = 6.9 Hz, 6H), 0.98 (dd, J = 6.8, 3.1 Hz, 6H).

[0073] .

[0074] S7: Under nitrogen atmosphere, the product obtained in the previous step, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone (248.4 mg, 1.15 mmol) was dissolved in Benzene (5 mL), and tetrachlorobenzoquinone (309.8 mg, 1.26 mmol) was added. The temperature was raised to 80 °C and stirred for 3 h. After the reaction was completed, water (10 mL) and ethyl acetate (10 mL x 5) were added to the reaction system for extraction. The organic phases were combined, washed with saturated brine (8 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and flash column chromatography with PE / EA = 100:1~20:1 was performed to obtain a white solid. 14 C-2,6-Diisopropylnaphthalene (111.2 mg, 0.52 mmol, 45% yield): 1 H NMR (400 MHz, DMSO-d6)δ 7.79 (d, J = 8.4 Hz, 2H), 7.69 – 7.65 (m, 2H), 7.41 (dd, J = 8.4, 1.7 Hz,2H), 3.04 (p, J = 6.9 Hz, 2H), 1.30 (d, J = 6.8 Hz, 12H). GC-MS: 214.1.

[0075] .

[0076] The synthesized 14C-2,6-diisopropylnaphthalene was tested to obtain the nuclear magnetic hydrogen spectrum of 2,6-diisopropylnaphthalene labeled with carbon-14 of the naphthalene ring. Figure 2 As shown, we get 14 The HPLC chromatogram of C-2,6-diisopropylnaphthalene is as follows Figure 3 As shown, the test conditions of the HPLC chromatogram are: detection wavelength: 254 nm, injection volume 10 μL, and it can be seen that its chemical purity is 98.67%.

[0077] The interpretation of the HPLC chromatogram is shown in Table 1 below: Table 1 Peak results table .

[0078] It is to be understood that the term "one" should be understood as "at least one" or "one or more", that is, in one embodiment, the number of an element may be one, while in another embodiment, the number of the elements may be multiple, and the term "one" should not be understood as a limitation on the quantity.

[0079] The present invention is not limited to the above-mentioned optimal implementation mode. Anyone can derive other forms of products under the inspiration of the present invention. However, no matter what changes are made in the shape or structure, any technical solution that is the same or similar to that of the present application falls within the scope of protection of the present invention.

Claims

1. A method for synthesizing 2,6-diisopropylnaphthalene labeled with 14 carbon atoms of the naphthalene ring, characterized in that: The following steps are involved: S1: Synthesis of 1-{2-[(1- 14 C) cyanomethyl]-3-methylbutyl}-4-isopropylbenzene; Under the protection of inert gas, 1-[2-(iodomethyl)-3-methylbutyl]-4-isopropylbenzene was reacted with 14 C-sodium cyanide is dissolved in an aprotic solvent and an inorganic base is added and stirred to react to obtain 1-{2-[(1- 14 C) cyanomethyl]-3-methylbutyl}-4-isopropylbenzene; S2: Synthesis of 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate; Under the protection of inert gas, 1-{2-[(1- 14 C) 3-[(4-isopropylphenyl)methyl]-4-methyl-1-[1-[(4-isopropylphenyl)methyl]-3-methylbutyl]-4-isopropylbenzene is dissolved in an alcohol solvent and an acid solvent is added and stirred to react to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl-1-[1- 14 C] ethyl valerate; S3: Synthesis of 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]valeric acid; Under the protection of inert gas, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] ethyl valerate was dissolved in a polar solvent and an inorganic base was added and stirred to obtain 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C]valeric acid; S4: Synthesis of 3,7-diisopropyl-[1- 14 C]-tetralone; Under the protection of inert gas, 3-[(4-isopropylphenyl)methyl]-4-methyl[1- 14 C] valeric acid is dissolved in an acid solution and dehydrated, and stirred at high temperature to react to obtain 3,7-diisopropyl-[1- 14 C]-tetralone; S5: Synthesis of 3,7-diisopropyl-[1- 14 C]-Tetrahydronaphthol: Under the protection of inert gas, 3,7-diisopropyl-[1- 14 C]-tetralone is dissolved in an aprotic solvent and a reducing agent is added, and the reaction is stirred at low temperature to obtain 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol; S6: Synthesis of 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone; Under the protection of inert gas, 3,7-diisopropyl-[1- 14 C]-tetrahydronaphthol is dissolved in an aprotic solvent, an acid solution is added to catalyze and dehydrate, and the reaction is stirred at high temperature to obtain 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone; S7: Synthesis 14 C-2,6-diisopropylnaphthalene: Under the protection of inert gas, 3,7-diisopropyl-[1- 14 C]-3,4-2H-naphthone is dissolved in an aprotic solvent, an oxidant is added for oxidation, and the reaction is stirred at high temperature to obtain 14 C-2,6-diisopropylnaphthalene.

2. The synthetic method of naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene according to claim 1, characterized in that, In step S1, the aprotic solvent is selected from one or any combination of DMSO, DMF, and THF.

3. The synthetic method of naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene according to claim 1, characterized in that, In step S1, the inorganic base is selected from one or any combination of LiOH, NaOH, and KOH.

4. The synthetic method of naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene according to claim 1, characterized in that, In step S2, the alcohol solvent is selected from one or any combination of MeOH, EtOH, and n-BuOH, and the acid solvent is selected from one or any combination of SOCl2, H2SO4, and HCl.

5. The synthetic method of naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene according to claim 1, characterized in that, In step S3, the polar solvent is selected from one or any combination of MeOH, EtOH, H2O, THF, and dioxane, and the inorganic base is selected from one or any combination of LiOH, NaOH, and KOH.

6. The synthetic method of naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene according to claim 1, characterized in that, In step S4, the acid solution is selected from one or any combination of H2SO4, PPA, and TsOH.

7. The method for synthesizing 2,6-diisopropylnaphthalene labeled with 14 carbon atoms of the naphthalene ring according to claim 1, wherein: In step S5, the aprotic solvent is selected from one or any combination of Et2O, THF, and 2-Me-THF, and the reducing agent is selected from one or any combination of LiBHEt3, NaBH4, and LiAlH4.

8. The method for synthesizing 2,6-diisopropylnaphthalene labeled with 14 carbon atoms of the naphthalene ring according to claim 1, wherein: In step S6, the aprotic solvent is selected from one or any combination of Toluene, THF, and 2-Me-THF, and the acid solution is selected from one or any combination of H2SO4, PPA, and TsOH.

9. The method for synthesizing 2,6-diisopropylnaphthalene labeled with 14 carbon atoms of the naphthalene ring according to claim 1, wherein: In step S7, the aprotic solvent is selected from one or any combination of Toluene, Benzene, and DCE, and the oxidant is selected from one or any combination of anthraquinone-2-sulfonate sodium, tetrachlorobenzoquinone, and 4-phenylpyridine-N-oxide.

10. A naphthalene ring carbon-14 labeled 2,6-diisopropylnaphthalene, characterized in that According to the synthesis method of any one of claims 1 to 9, 2,6-diisopropylnaphthalene labeled with carbon-14 of the naphthalene ring is synthesized, and the structural formula is shown in the following formula (I): 。

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