A method for synthesizing 2-phosphinobenzothiazoles

Abstract

The application belongs to the technical field of chemistry and chemical industry, and particularly relates to a synthesis method of 2-phosphyl benzothiazole compounds. The synthesis method uses 2-iodo aryl isothiocyanate and pentavalent PH organic phosphorus reagent as substrates, and realizes rapid and efficient synthesis of 2-phosphyl benzothiazole compounds under green reaction conditions without using transition metal or ligand catalysis through conventional heating or microwave promotion. The synthesis method has the advantages of mild and environment-friendly conditions, cheap and easily available raw materials, wide substrate sources, fast reaction speed and high product yield. The benzothiazole five-membered heterocyclic structure efficiently constructed by the application is a core skeleton of numerous organic ligands, medicines and flame-retardant materials.

Description

Technical Field

[0001] This invention belongs to the field of chemical engineering technology, specifically relating to a method for synthesizing 2-phosphobenzothiazole compounds, which is widely used in the synthesis of chemicals in the fields of biochemistry, materials chemistry, and catalysis. Background Technology

[0002] 2-Phosphobenzothiazoles have become an important research subject in the fields of chemistry, medicine, and materials due to their unique biological activity and physicochemical properties. They can be widely used as phosphine ligands in catalysis, as analgesics, and possess potential anti-proliferative, anti-inflammatory, and anti-tuberculosis activities. For example, Chinese patent CN119798326A describes 2-arylphosphosylbenzothiazole compounds that exhibit good inhibition rates against tomato gray mold and certain fungicidal activity. Furthermore, in 2024, Professor Mingjun Chen of Xihua University (Fu, ZC; Feng, LP; Chen, MJ et al.) Org. Chem. Front. 2024 11 , 270) reported 2-diphenylphosphonobenzothiazole, which has good flame retardant properties and can be used as a flame retardant material.

[0003] To date, there are two main synthetic methods for constructing the 2-phosphobenzothiazole skeleton: dehydrogenation cross-coupling reaction of benzothiazole and radical coupling cyclization reaction based on 2-isocyanoaryl sulfide.

[0004] One is the dehydrogenation cross-coupling reaction of benzothiazole.

[0005] The dehydrogenation cross-coupling reaction of benzothiazole catalyzed by metal catalysts or oxidants is a traditional method for synthesizing 2-phosphobenzothiazole. In 2012, the Li Fuwei research group (Hou, CD; Ren, YL; Lang, R.; Hu, XX; Xia, CG; Li, FW) Chem. Commun., 2012 , 48, (5181-5183.) reported a palladium-catalyzed phosphonylation reaction of benzothiazoles with dialkyl phosphites for the efficient synthesis of 2-phosphobenzothiazole compounds. This reaction has a broad substrate range, but requires excessively high temperatures and long reaction times.

[0006] In 2014, Chen Xiaolan and her team (Chen X.-L.; Li X.; Qu L.-B., et al.) J. Org. Chem. ,2014, 79(8407-8416) A series of 2-phosphobenzothiazole compounds were synthesized in yields ranging from 62% to 86% by using di-tert-butyl peroxide (DTBP) as an initiator and benzothiazole and dialkyl phosphite or diarylphosphine oxide as substrates.

[0007] In 2015, Zhang Huijun and her colleagues (Zhang H.-J.; Lin W.; Wu Z., et al.) Chem. Commun. ,2015, 51 (3450-3453.) A silver-mediated direct phosphonylation method for benzothiazole and thiazole was developed. This method uses benzothiazole and diphenylphosphine oxide as substrates, requires no additional oxidant, and proceeds under AgNO3 catalysis to yield 2-phosphonylbenzothiazole. This reaction exhibits good functional group compatibility and substrate universality, but its effectiveness is limited for other H+ groups. P-structured substrates, such as dialkyl phosphites, hypophosphites, and aliphatic dialkylphosphine oxides, each had only one example and low yields. Moreover, the reaction still required high temperatures and had a long reaction time.

[0008] In 2016, Wu Lei and his team (Luo K.; Chen L.-X.; Wu L.) J. Org. Chem. ,2016, 81 (4682-4689.) The authors successfully applied auto-oxidative coupling to the construction of C(sp²)-P bonds, pioneering a new method for the direct phosphonylation of heteroaromatic hydrocarbons under metal-free and solvent-free conditions. The reaction used benzothiazole and diarylphosphine oxides as substrates and was carried out in an oxygen-rich environment, successfully synthesizing various 2-phosphonylbenzothiazole compounds in yields ranging from 21% to 97%. Furthermore, the authors also attempted to synthesize diethyl phosphite and aliphatic phosphine oxides, but were unable to obtain the corresponding target products.

[0009] In the same year, Wu Lei's research group (Luo K.; Chen Y.-Z.; Wu L., et al.) Org. Lett. ,2016, 18 (452-455.) Another metal-free C catalyst catalyzed by visible light was developed. H-functionalization reaction, applied to heterocyclic C(sp²) Construction of P-bonds. This method uses benzothiazole and diarylphosphine oxides as substrates, employs Eosin B as a photocatalyst, and proceeds under conditions without external oxidants, successfully synthesizing various 2-phosphonobenzothiazole compounds in medium to excellent yields. Furthermore, the authors also attempted to synthesize aliphatic phosphine oxides, but were unable to obtain the corresponding target products.

[0010] In 2017, Zhang Huijun's research group (Lin W.; Su F.; Wen T.-B.; Zhang H.-J.) Eur. J. Org. Chem. ,2017, 2017 (1757-1759.) developed a K2S2O8 (potassium persulfate)-promoted (benzothiazole) C The H-phosphorylation method, using benzothiazole and diarylphosphine oxides as substrates, achieves C-phosphorylation via a radical pathway without the need for transition metal catalysis. Direct phosphonylation with H was also attempted. In addition, the authors tried substrates such as diethyl phosphite and aliphatic phosphine oxides, but the yields were low and examples were few; the product yield of ethyl phenylphosphite substrate was only 32%.

[0011] In the same year, Gong J., Huang L., Deng Q., et al. Org. Chem. Front. ,2017, 4 (9): 1781-1784.) A metal-free phosphonylation method was developed for the C-phase synthesis of benzoxazole and benzothiazole. H-phosphonylation. This method utilizes iodine (I₂) and potassium persulfate (K₂S₂O₈) as oxidants, and the reaction is carried out in acetonitrile solvent. It exhibits good applicability to various benzoxazole and benzothiazole derivatives, as well as trialkyl phosphates with different substituents, with yields ranging from 46% to 79%.

[0012] In 2019, Singh et al. (Hore S.; Srivastava A.; Singh R., et al.) J. Org. Chem. ,2019, 84 (11): 6868-6878.) A copper-catalyzed oxidation of potassium persulfate (K2S2O8) via benzothiazole C(sp) was developed. 2 ) H and dialkyl phosphite P(O) H directly couples to form C The P-bond method yields between 36% and 67%.

[0013] In 2024, Jiang Zeqi's research group (Jiang Z.; Jiang S.; Zhang X., et al.) Green Chem. 2024 26 (9): 5538-5545.) Molybdenum oxide ([N(C4H9)4]2[Mo6O) supported by inorganic ligands 19 []) as a hydrogen atom transfer (HAT) photocatalyst, the phosphonylation reaction of benzothiazole and arylphosphine oxide under visible light was realized. This method can be carried out at room temperature in an aqueous solvent medium without the need for additional metals, bases, additives or external oxidants, and has excellent functional group tolerance.

[0014] Second, the free radical coupling cyclization reaction of 2-isocyanoaryl sulfides.

[0015] In recent years, isocyanates, as multifunctional building blocks, have not only participated in reactions as nucleophiles but also served as effective radical acceptors and intermediates for the generation of imine radicals, playing a crucial role in radical cyclization reactions. Based on the radical coupling cyclization reaction of 2-isocyanoaryl sulfides, this approach has been successively developed and applied to the synthesis of 2-phosphobenzothiazoles. In 2018, Wu Lei and his research team (Yang W.-C.; Zhu J.; Wu L., et al.) Org. Lett. ,2018, 20 (10): 3144-3147.) A novel method for synthesizing 2-phosphonobenzothiazole via a radical cyclization reaction was developed. This method involves reacting 2-isocyanoaryl sulfides with phosphine oxides or phosphite substrates under Mn(OAc)3 catalysis, achieving imine radical addition from the isocyanate to the sulfur atom, thus efficiently constructing 2-phosphonobenzothiazole. However, only two examples of dialkyl phosphite substrates were given: dimethyl phosphite and diisopropyl phosphite, with low yields.

[0016] In 2020, Yang Wenchao's research group (Yang W.; Lia B.; Zhang M., et al.) Chin. Chem. Lett. 2020 31(5): 1313-1316.) A metal-free, photo-induced radical reaction method for constructing C–P and C–S bonds was first realized. This method achieved C(sp) bonds through a visible light-promoted phosphonylation reaction of 2-isocyanoaryl sulfides. 3 The authors investigated the breaking of the C–S bond and the formation of the imine C–S bond. They also tried two dialkyl phosphites and one aliphatic phosphine oxide substrate, but failed to obtain the desired product.

[0017] In 2021, Chen Xiaolan's team (Chen X.-L.; Liu Y.; Li X.-Y., et al.) J. Am. Chem. Soc. 2021 143 (2): 964-972.) Developed 2,4,5,6-tetra(3,6-di-tert-butyl-9 H -Carbazole-9-yl)isophthalonitrile(4CzIPN- t Using Bu as a photocatalyst, 2-phosphonobenzothiazole was successfully synthesized from 2-isocyanoaryl sulfide and diarylphosphine oxide via a visible light-induced proton-coupled electron transfer (PCET) reaction.

[0018] In 2022, Wu Lizhu's team (Yu J.-X.; Cheng Y.-Y.; Wu L.-Z., et al.) Angew. Chem. Int. Ed. 2022 61 (e202209293.) Using cobalt oxime as a photocatalyst, a series of 2-phosphobenzothiazoles were efficiently constructed by reacting 2-isocyanoaryl sulfides with diphenylphosphine oxides under visible light irradiation via phosphorus radical addition and intramolecular cyclization. Various substituted diphenylphosphine oxides and 2-isocyanoaryl sulfides reacted smoothly with good to excellent yields (up to 97%). Furthermore, the authors provided two examples using diethyl phosphite and ethyl arylphosphite as substrates, with yields of 44% and 63%, respectively.

[0019] In 2023, Zhu Jie's research group (Zhu P.-W.; Ma H.-M.; Zhu J., et al.) J. Org. Chem. 2023 88(4): 2069-2078.) reported an electrochemically triggered cascade cyclization strategy for the efficient synthesis of 2-phosphonobenzothiazoles. This method uses 2-isocyanoaryl sulfide and diarylphosphine oxide as substrates, directly generating a phosphorus-centered radical via anodic oxidation, followed by an addition reaction with an isocyanate group, leading to the intramolecular cyclization synthesis of 2-phosphonobenzothiazole compounds. The authors also attempted reactions with dimethylphosphine oxide and diethyl phosphite substrates, but failed to obtain the corresponding target product.

[0020] In addition to the above-mentioned free radical coupling cyclization reaction method based on 2-isocyanoaryl sulfides, Hao Wenyan's research group (Wang H.; Huang L.; Li J.; Hao W.) in 2023. Org. Biomol. Chem. 2023 21 (38): 7696-7701.) reported a copper(II)-catalyzed cascade of isothiocyanates, C(sp...) 2 This reaction involves the formation of α-P / C-C bonds. Using o-haloaryl isothiocyanates and phosphites as substrates, it achieves the efficient synthesis of 2-phosphonobenzothiazoles under mild conditions. In the template reaction, replacing the 2-iodophenyl isothiocyanate substrate with 2-chloro or 2-bromo resulted in product yields of 78% and 18%, respectively. Furthermore, attempts to use diphenylphosphine oxide as a substrate were unsuccessful. The substrate scope for this reaction is quite limited, with only dialkyl phosphites suitable, and it is transition metal-dependent.

[0021] In summary, although the synthetic methods for 2-phosphotenthiazole have been continuously updated, many problems still exist. On the one hand, the dehydrogenation cross-coupling reaction usually requires the use of expensive metal catalysts and ligands, which not only increases economic costs but also limits its industrial production application. On the other hand, the radical coupling cyclization reaction is time-consuming, resulting in poor efficiency and energy consumption for large-scale synthesis.

[0022] Therefore, there is a need to develop a new synthetic method for 2-phosphobenzothiazole that does not require transition metal / ligand catalysis, is fast, operates under mild conditions, uses inexpensive raw materials, and is applicable to various pentavalent phosphorus substrates such as phosphites ((RO)2PHO), phosphonites (R(OR')PHO), and secondary phosphine oxides (R2PHO). Summary of the Invention

[0023] This method develops a transition metal / ligand-free tandem reaction strategy that enables the rapid and efficient synthesis of 2-phosphobenzothiazoles with diverse structures under mild conditions, starting from inexpensive and readily available raw materials.

[0024] The technical solution adopted in this invention is as follows: This invention provides a method for synthesizing 2-phosphobenzothiazole, using 2-iodoaryl isothiocyanate and H-P substrate as raw materials, cesium carbonate (Cs2CO3) as base, ester as solvent, and reacting at 60-90 °C. The reaction formula is as follows: In the reaction formula, R 1 Including but not limited to: hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen or trifluoromethyl; R 2 R 3 Including but not limited to: C1-C6 alkoxy, C1-C6 alkyl, C3-C7 cycloalkyl, and optionally substituted aryl groups; the substituents of the optionally substituted aryl groups include halogens, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, and trifluoromethyl groups; or R 2 and R 3 Together with the phosphorus atoms to which they are attached, they form a 5- to 14-membered ring system selected from those having 1 phosphorus heteroatom and 0 to 2 oxygen heteroatoms, which may be either monocyclic or fused ring.

[0025] Preferably, the synthesis method comprises the following steps: adding 2-iodoaryl isothiocyanate, H-P substrate and cesium carbonate into a container, adding solvent, and heating the reaction until the starting materials disappear.

[0026] Furthermore, after the reaction is complete, saturated NH4Cl is added to quench the reaction.

[0027] Furthermore, the product was extracted with an ester solvent and then purified by column chromatography to obtain the target product, 2-phosphotenthiazole. Preferably, the molar ratio of 2-iodoaryl isothiocyanate, H-P substrate, and cesium carbonate is 1:(1.1~1.3):(1.8~2.2).

[0028] Preferably, the 2-iodoaryl isothiocyanate includes 2-iodophenyl isothiocyanate, 2-iodo-4-methylphenyl isothiocyanate, 2-iodo-5-methylphenyl isothiocyanate, 2-iodo-3-methylphenyl isothiocyanate, 2-iodo-4,5-dimethylphenyl isothiocyanate, 2-iodo-4-methoxyphenyl isothiocyanate, 2-iodo-4-fluorophenyl isothiocyanate, 2-iodo-4-chlorophenyl isothiocyanate, 2-iodo-4-bromophenyl isothiocyanate, 2,4-diiodophenyl isothiocyanate, 2-iodo-4-trifluoromethylphenyl isothiocyanate, and 2-iodo-naphthyl isothiocyanate.

[0029] Preferably, the HP substrate is in R 2 and R 3In the case where the phosphorus atoms to which they are attached are not cyclic, these include phosphite diesters, secondary phosphine oxides, and phosphite esters.

[0030] Further, the phosphite diesters include dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, and di-n-butyl phosphite; secondary phosphine oxides include dimethylphosphine oxide, di-n-butylphosphine oxide, dicyclohexylphosphine oxide, diphenylphosphine oxide, bis(4-methylphenyl)phosphine oxide, bis(2-methylphenyl)phosphine oxide, bis(3,5-dimethylphenyl)phosphine oxide, bis(4-methoxyphenyl)phosphine oxide, bis(4-tert-butylphenyl)phosphine oxide, bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine oxide, bis(4-phenylphenyl)phosphine oxide, bis(4-fluorophenyl)phosphine oxide, bis(4-chlorophenyl)phosphine oxide, bis(4-bromophenyl)phosphine oxide, and bis(4-trifluoromethylphenyl)phosphine oxide; and phosphite esters include ethyl phenylphosphite.

[0031] Preferably, the HP substrate is in R 2 and R 3 When cyclically formed with the phosphorus atoms to which they are attached, they include 5,5-dimethyl-1,3,2-dioxophosphacyclohexane-2-oxide and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide.

[0032] The beneficial effects of this invention are as follows: This reaction uses 2-iodoaryl isothiocyanate and H-P substrate as raw materials, and only requires the addition of cesium carbonate (Cs₂CO₃) and heating to efficiently synthesize 2-phosphobenzothiazole compounds. Compared with the prior art, the synthetic method of this invention has the following advantages: (1) The synthesis method described in this invention has a very fast reaction rate, requiring only 1 hour, and the conversion rate of most products is close to quantitative. (2) The synthesis method described in this invention does not require transition metal catalysis or the participation of other ligands, and the reaction conditions are mild and environmentally friendly; (3) The synthesis method described in this invention has a wide range of applicable substrates, covering three typical types of pentavalent phosphorus substrates (phosphite diester, phosphonite ester, and secondary phosphine oxide), thus obtaining a variety of product structure types; (4) The synthesis method described in this invention uses inexpensive raw materials, does not require inert gas protection for the reaction, and is not sensitive to air humidity.

[0033] The 2-phosphobenzothiazole efficiently constructed in this invention is an important backbone for many bioactive molecules and functional materials. The synthesis method described in this invention provides a universal method for the synthesis and preparation of such compounds. Detailed Implementation

[0034] Example 1 Synthesized from 2-iodophenyl isothiocyanate (1a) and dimethyl phosphite (2a): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of dimethyl phosphite (2a) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a yellow oily liquid with a yield of 96%.

[0035] Yellow, oily liquid. f = 0.5 (ethyl acetate / n-hexane = 1:1); 70.0 mg,96%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.19 (d, J = 7.7 Hz, 1H), 7.96 (d, J = 7.5Hz, 1H), 7.57 – 7.44 (m, 2H), 3.89 (d, J = 11.4 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 157.54 (d, J = 238.5 Hz), 153.48 (d, J = 28.5 Hz), 135.37 (d, J =1.5 Hz), 126.21, 125.96, 124.03, 121.03 (d, J = 1.5 Hz), 53.19 (d, J = 6 Hz). 31 PNMR (121 MHz, Chloroform- d δ 6.75. HRMS (ESI) m / z [M + H] + Calcd for C9H 11 NO3PS + 244.0192; Found: 244.0194. Example 2 Synthesized from 2-iodophenyl isothiocyanate (1a) and diethyl phosphite (2b): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and the solvent was evaporated to obtain the pure product, which was a yellow oily liquid with a yield of 99%.

[0036] Yellow, oily liquid. f = 0.5 (ethyl acetate / n-hexane = 1:1); 80.5mg,99%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.17 (d, J = 7.1 Hz, 1H), 7.93 (d, J = 6.9Hz, 1H), 7.54 – 7.40 (m, 2H), 4.35 – 4.16 (m, 4H), 1.32 (t, J = 7.1 Hz, 6H). 13 CNMR (75 MHz, Chloroform- d ) δ 155.98 (d, J = 237.0 Hz), 154.96 (d, J = 28.5 Hz), 136.43 (d, J = 1.5 Hz), 126.99, 126.89, 126.86, 124.91, 121.98 (d, J = 1.5 Hz), 64.13 (d, J = 5.3 Hz), 16.32 (d, J = 6.8 Hz). 31 P NMR (121 MHz, Chloroform- d δ4.06. HRMS (ESI) m / z [M + H] + Calcd for C 11 H 15 NO3PS +272.0505; Found: 272.0509. Example 3 Synthesized from 2-iodophenyl isothiocyanate (1a) and diisopropyl phosphite (2c): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of diisopropyl phosphite (2c) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 98%.

[0037] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);87.9mg, 98%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.17 (d, J = 7.0 Hz, 1H), 7.94 (d, J = 6.8 Hz, 1H), 7.55 – 7.41 (m, 2H), 4.92 – 4.77 (m, 2H), 1.36 (d, J = 6.2 Hz, 6H), 1.27 (d, J = 6.2 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 161.54 (d, J =237.8 Hz), 154.61 (d, J = 28.5 Hz), 136.54, 126.87, 126.69, 124.98, 121.92 (d, J = 10.5 Hz), 73.33 (d, J = 6 Hz), 24.12 (d, J = 4.5 Hz), 23.79 (d, J = 5.3 Hz). 31 PNMR (121 MHz, Chloroform- d ) δ 1.99. HRMS (ESI) m / z [M + H] + Calcd forC 13 H 19 NO3PS + 300.0818; Found: 300.0821. Example 4 Synthesized from 2-iodophenyl isothiocyanate (1a) and di-n-butyl phosphite (2d) as raw materials (3d): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of di-n-butyl phosphite (2d) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 98%.

[0038] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);96.2mg, 98%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.16 (d, J = 7.2 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.55 – 7.38 (m, 2H), 4.27 – 4.07 (m, 4H), 1.70 – 1.56 (m,4H), 1.40 – 1.28 (m, 4H), 0.83 (t, J = 7.4 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 158.89 (d, J = 237.0 Hz), 153.53 (d, J = 28.5 Hz), 135.31, 125.98, 125.82,123.93, 120.88 (d, J = 1.5 Hz), 66.71 (d, J = 6.0 Hz), 31.32 (d, J = 6.0 Hz), 17.61, 12.54.31 P NMR (121 MHz, Chloroform- d 4.18. HRMS (ESI) m / z [M + H] + Calcd for C 15 H 23 NO3PS + 328.1131; Found: 328.1135. Example 5 Synthesized from 2-iodophenyl isothiocyanate (1a) and cyclic 5,5-dimethyl-1,3,2-dioxophosphazenecyclohexane-2-one (2e) (3e): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of 5,5-dimethyl-1,3,2-dioxophosphazenecyclohexane-2-one (2e) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow oily liquid with a yield of 75%.

[0039] Yellow, oily liquid. f = 0.5 (ethyl acetate / n-hexane = 1:1); 63.7mg,75%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.13 (d, J = 7.2 Hz, 1H), 7.95 (d, J = 6.8Hz, 1H), 7.55 – 7.42 (m, 2H), 4.69 (d, J = 10.8 Hz, 2H), 4.02 (dd, J = 20.3, 11.1Hz, 2H), 1.35 (s, 3H), 0.92 (s, 3H). 13 C NMR (75 MHz, Chloroform- d ) δ 159.13(d, J = 230.3 Hz), 153.31 (d, J = 28.5 Hz), 134.79 (d, J= 2.3 Hz), 126.01, 125.78,123.63, 121.09 (d, J = 1.5 Hz), 77.62 (d, J = 7.5 Hz), 31.83 (d, J = 7.5 Hz), 21.10, 19.47. 31 P NMR (121 MHz, Chloroform- d δ -4.60. HRMS (ESI) m / z [M + H] + Calcd for C 12 H 15 NO3PS + 284.0505; Found: 284.0506. Example 6 Synthesized from 2-iodophenyl isothiocyanate (1a) and dimethylphosphine oxide (2f): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of dimethylphosphine oxide (2f) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product as a yellow oily liquid with a yield of 66%.

[0040] Yellow, oily liquid. f = 0.5 (ethyl acetate / n-hexane = 1:1); 41.8mg,66%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.09 (d, J = 7.5 Hz, 1H), 7.98 (d, J = 7.1Hz, 1H), 7.55 – 7.42 (m, 2H), 1.90 (d, J = 13.8 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 166.89 (d, J = 120.0 Hz), 153.73 (d, J= 21.0 Hz), 135.68,125.79, 125.67, 123.31, 121.29, 16.99 (d, J = 73.5 Hz). 31 P NMR (121 MHz, Chloroform- d ) δ 35.41. HRMS (ESI) m / z [M + H] + Calcd for C9H 11 NOPS + 212.0293; Found: 212.0295. Example 7 Synthesized (3g) using 2-iodophenyl isothiocyanate (1a) and dibutylphosphine oxide (2g) as raw materials: 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of dibutylphosphine oxide (2 g) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a white solid with a yield of 70%.

[0041] White solid; mp: 84.5 – 86.1 ℃. R f = 0.5 (ethyl acetate / n-hexane =1:1); 62.0 mg, 70%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.10 (d, J = 7.4 Hz, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.56 – 7.39 (m, 2H), 2.17 – 2.01 (m, 4H), 1.74 – 1.57(m, 2H), 1.51 – 1.27 (m, 6H), 0.81 (t, J = 7.2 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.64 (d, J = 108.0 Hz), 154.97 (d, J= 19.5 Hz), 136.91,126.72, 126.43, 124.31, 122.28, 29.76 (d, J = 69.0 Hz), 24.03 (d, J = 15.0 Hz), 23.41 (d, J = 4.5 Hz), 13.62. 31 P NMR (121 MHz, Chloroform- d ) δ 42.49. HRMS (ESI) m / z [M + H] + Calcd for C 15 H 23 NOPS + 296.1232; Found: 296.1235. Example 8 Synthesized (3h) using 2-iodophenyl isothiocyanate (1a) and dicyclohexylphosphine oxide (2h) as starting materials: 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of dicyclohexylphosphine oxide (2h) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a colorless solid with a yield of 68%.

[0042] Colorless solid; mp:163.8 – 164.5 ℃. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 70.8mg, 68%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.13 (d, J = 7.6Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.47 (dq, J = 13.7, 7.2 Hz, 2H), 2.28 – 2.04(m, 4H), 1.82 – 1.48 (m, 11H), 1.24 – 1.05 (m, 7H). 13C NMR (75 MHz, Chloroform- d ) δ 165.94 (d, J = 98.3 Hz), 154.21 (d, J = 18.8 Hz) 135.83, 125.38,125.09, 123.29, 121.11, 35.11 (d, J = 66.8 Hz), 25.34 (d, J = 4.5 Hz), 25.13 (d, J = 4.5 Hz), 24.68 (d, J = 1.5 Hz), 24.03 (d, J = 3.0 Hz), 23.64 (d, J = 3.8 Hz). 31 PNMR (121 MHz, Chloroform- d ) δ 47.13. HRMS (ESI) m / z [M + H] + Calcd forC 19 H 27 NOPS + 348.1545; Found: 348.1549. Example 9 Synthesized from 2-iodophenyl isothiocyanate (1a) and diphenylphosphine oxide (2i) as raw materials (3i): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of diphenylphosphine oxide (2i) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a white solid with a yield of 96%.

[0043] White solid; mp: 165.3 – 167.1 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 96.5 mg, 96%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.11 (d, J= 8.1 Hz, 1H), 7.88 (dd, J = 13.1, 7.1 Hz, 5H), 7.44 (dd, J = 17.9, 7.1 Hz, 8H). 13 C NMR (75 MHz, Chloroform- d ) δ 166.83 (d, J = 126.8 Hz), 155.39 (d, J = 21.0 Hz), 136.77, 132.72 (d, J = 3.0 Hz), 132.03 (d, J = 10.5 Hz), 131.01 (d, J = 108.8 Hz), 128.72 (d, J =12.8 Hz) 126.67 (d, J = 3.8 Hz), 124.79, 122.19. 31 P NMR (121 MHz, Chloroform- d 20.16. HRMS (ESI) m / z [M + H] + Calcd for C 19 H 15 NOPS + 336.0606; Found: 336.0610. Example 10 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(p-tolyl)phosphine oxide (2j): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(p-tolyl)phosphine oxide (2j) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 96%.

[0044] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);104.6mg, 96%. 1H NMR (300 MHz, Chloroform- d ) δ 8.08 (d, J = 7.8 Hz, 1H), 7.90(d, J = 7.7 Hz, 1H), 7.74 (dd, J = 12.5, 8.1 Hz, 4H), 7.47 – 7.35 (m, 2H), 7.20(dd, J = 8.1, 3.0 Hz, 4H), 2.30 (s, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.39(d, J = 126.0 Hz), 155.37 (d, J = 21.0 Hz), 143.31 (d, J = 3.0 Hz), 136.78, 132.03 (d, J = 10.5 Hz), 129.41 (d, J = 12.8 Hz), 127.82 (d, J = 111.0 Hz), 126.61 (d, J =5.3 Hz), 124.73, 122.09, 21.68 (d, J = 1.5 Hz). 31 P NMR (121 MHz, Chloroform- d δ20.91. HRMS (ESI) m / z [M + H] + Calcd for C 21 H 19 NOPS + 364.0919; Found: 364.0923. Example 11 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(2-methylphenyl)phosphine oxide (2k): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(2-methylphenyl)phosphine oxide (2k) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow solid with a yield of 94%.

[0045] Yellow solid; mp: 176.9 – 178.5 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 102.4mg, 94%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.17 (d, J = 7.1 Hz, 1H), 8.02 (d, J = 7.7 Hz, 1H), 7.57 – 7.41 (m, 6H), 7.31 – 7.19 (m, 4H), 2.54 (s, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.83 (d, J = 124.5 Hz), 155.21 (d, J = 21.0Hz), 143.23 (d, J = 9.0 Hz), 137.31, 132.94 (d, J = 12.8 Hz), 132.70 (d, J = 3.0Hz), 131.97 (d, J = 11.3 Hz), 129.41 (d, J = 105.8 Hz), 126.72, 125.84 (d, J = 13.5Hz), 124.91, 122.23, 21.82 (d, J = 4.5 Hz). 31 P NMR (121 MHz, Chloroform- d δ27.29. HRMS (ESI) m / z [M + H] + Calcd for C 21 H 19NOPS + 364.0919; Found: 364.0922. Example 12 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(3,5-dimethylphenyl)phosphine oxide (2l): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(3,5-dimethylphenyl)phosphine oxide (2l) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow solid with a yield of 98%.

[0046] Yellow solid; mp: 173.7 – 174.8 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 115.0mg, 98%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.10 (d, J = 7.5 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.51 – 7.32 (m, 6H), 7.07 (s, 2H), 2.22 (s, 12H). 13 CNMR (75 MHz, Chloroform- d ) δ 166.41 (d, J = 124.5 Hz), 154.42 (d, J = 21.0 Hz), 137.43 (d, J = 13.5 Hz), 135.81, 133.42 (d, J = 3.0 Hz), 129.58 (d, J = 106.5 Hz), 128.37 (d, J = 9.8 Hz), 125.53 (d, J = 5.5 Hz), 123.71, 121.03, 20.30. 31 P NMR (121MHz, Chloroform- d) δ 21.32. HRMS (ESI) m / z [M + H] + Calcd for C 23 H 23 NOPS + 392.1232; Found: 392.1236. Example 13 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-methoxyphenyl)phosphine oxide (2m): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-methoxyphenyl)phosphine oxide (2m) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 97%.

[0047] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);115.0mg, 97%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.08 (d, J = 8.0 Hz, 1H), 7.90(d, J = 7.8 Hz, 1H), 7.77 (dd, J = 12.1, 8.5 Hz, 4H), 7.49 – 7.33 (m, 2H), 6.90(d, J = 6.2 Hz, 4H), 3.73 (s, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 166.83 (d, J =126.0 Hz), 161.91 (d, J = 3.0 Hz), 154.33 (d, J = 21.8 Hz), 135.68, 132.89 (d, J =12.0 Hz), 125.62 (d, J= 7.5 Hz), 123.57, 121.20 (d, J = 115.5 Hz), 121.02,113.21 (d, J = 14.3 Hz), 54.29. 31 P NMR (121 MHz, Chloroform- d ) δ 20.63. HRMS(ESI) m / z [M + H] + Calcd for C 21 H 19 NO3PS + 396.0818; Found: 396.0822. Example 14 Synthesizing (3n) from 2-iodophenyl isothiocyanate (1a) and bis(4-tert-butylphenyl)oxophosphine (2n): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-tert-butylphenyl)oxyphosphine (2n) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow solid with a yield of 88%.

[0048] Yellow solid; mp: 183.6 – 184.5 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 118.1mg, 88%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.19 (d, J = 7.4 Hz, 1H), 8.01 – 7.86 (m, 5H), 7.55 – 7.43 (m, 6H), 1.30 (s, 18H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.61 (d, J = 124.5 Hz), 156.10 (d, J = 3.0 Hz), 155.38 (d, J=21.8 Hz), 136.78, 131.92, 131.83, 127.80 (d, J = 111.0 Hz), 126.61 (d, J = 6.8Hz), 125.67 (d, J = 12.8 Hz), 124.69, 122.05, 35.08 (d, J = 1.5 Hz), 31.10. 31 P NMR (121 MHz, Chloroform- d ) δ 20.17. HRMS (ESI) m / z [M + H] + Calcd for C 27 H 31 NOPS + 448.1858; Found: 448.1859. Example 15 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(3,5-di-tert-butylphenyl)oxophosphine (2o): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(3,5-di-tert-butylphenyl)phosphine oxide (2o) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow solid with a yield of 83%.

[0049] Pale yellow solid; mp: 185.8 – 187.5 ℃. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 139.3mg, 83%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.08 (d, J = 7.5Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.80 (dd, J = 13.3, 1.8 Hz, 4H), 7.53 (s, 2H), 7.37 (dt, J= 18.1, 7.2 Hz, 2H), 1.21 (s, 36H). 13 C NMR (75 MHz, Chloroform- d ) δ167.12 (d, J = 122.3 Hz), 154.43 (d, J = 20.3 Hz), 149.86 (d, J = 12.0 Hz), 135.68,129.01 (d, J = 107.3 Hz), 125.73 (d, J = 3.0 Hz), 125.41, 125.23 (d, J = 11.3 Hz),123.51, 120.90, 34.11 (d, J = 1.5 Hz), 30.30. 31 P NMR (121 MHz, Chloroform- d δ20.94. HRMS (ESI) m / z [M + H] + Calcd for C 35 H 47 NOPS + 560.3110; Found: 560.3112. Example 16 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine (2p): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine oxide (2p) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow solid with a yield of 80%.

[0050] Pale yellow solid; mp: 188.2 – 189.6 ℃. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 148.6mg, 80%. 1H NMR (300 MHz, Chloroform- d ) δ 8.07 (d, J = 8.3Hz, 1H), 7.90 (d, J = 6.9 Hz, 1H), 7.82 (s, 2H), 7.77 (s, 2H), 7.45 – 7.31 (m,2H), 3.59 (s, 6H), 1.30 (s, 36H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.28 (d, J =122.3 Hz), 162.27 (d, J = 3.8 Hz), 154.41 (d, J = 21.0 Hz), 143.22 (d, J = 12.8Hz), 135.63, 129.71, 129.60, 125.39 (d, J = 13.5 Hz), 123.46 (d, J = 111.8 Hz),123.42, 121.03, 63.35, 35.01, 30.83. 31 P NMR (121 MHz, Chloroform- d ) δ 20.69.HRMS (ESI) m / z [M + H] + Calcd for C 37 H 51 NO3PS + 620.3322; Found: 620.3324. Example 17 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-phenylphenyl)oxophosphine (2q): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-phenylphenyl)phosphine oxide (2q) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a white solid with a yield of 69%.

[0051] White solid; mp: 92.5 – 94.2℃. R f = 0.5 (ethyl acetate / n-hexane =1:1); 100.8mg, 69%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.11 (d, J = 7.5 Hz, 1H),8.03 – 7.87 (m, 5H), 7.61 (dd, J = 8.3, 2.9 Hz, 4H), 7.49 – 7.23 (m, 12H). 13 CNMR (75 MHz, Chloroform- d ) δ 167.01 (d, J = 126.8 Hz), 155.52 (d, J = 21.8 Hz), 145.53 (d, J = 3.0 Hz), 139.79, 136.89, 132.55, 132.52, 129.58 (d, J = 109.5 Hz),129.01, 128.43, 127.61, 127.43, 126.81 (d, J = 5.3 Hz), 124.83, 122.21. 31 P NMR (121 MHz, Chloroform- d ) δ 20.09. HRMS (ESI) m / z [M + H] + Calcd for C 31 H 23 NOPS + 488.1232; Found: 488.1235. Example 18 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-fluorophenyl)phosphine oxide (2r): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-fluorophenyl)phosphine oxide (2r) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 3 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product as a pale yellow oily liquid with a yield of 56%.

[0052] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 62.3mg, 56%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.10 (d, J = 7.9 Hz, 1H), 7.95 – 7.83(m, 5H), 7.50 – 7.38 (m, 2H), 7.11 (td, J = 8.7, 2.4 Hz, 4H). 13 C NMR (75 MHz, Chloroform- d ) δ 167.32 (d, J = 3.8 Hz), 166.18 (d, J = 129.3 Hz), 163.87 (d, J =3.8 Hz), 155.31 (d, J = 21.8 Hz), 136.73, 134.51 (dd, J = 21.3 Hz), 127.61 (d, J =3.8 Hz), 126.90, 126.11 (d, J = 3.0 Hz), 124.82, 122.24, 116.31 (dd, J = 32.3, 7.5 Hz). 19 F NMR (282 MHz, Chloroform- d ) δ -104.86. 31 P NMR (121 MHz, Chloroform- d ) δ 18.52. HRMS (ESI) m / z [M + H] + Calcd for C 19H 13 F2NOPS + 372.0418; Found: 372.0420. Example 19 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-chlorophenyl)phosphine oxide (2s) (3s): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-chlorophenyl)phosphine oxide (2s) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 12 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product as a pale yellow oily liquid with a yield of 45%.

[0053] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);54.4mg, 45%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.20 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 6.7 Hz, 1H), 7.91 (dd, J = 12.2, 8.5 Hz, 4H), 7.61 – 7.46 (m, 6H). 13 C NMR (75MHz, Chloroform- d ) δ 165.72 (d, J = 129.8 Hz), 155.31 (d, J = 21.8 Hz), 139.58(d, J = 3.0 Hz), 136.69, 133.35, 133.21, 129.20 (d, J = 12.8 Hz), 129.21 (d, J =110.3 Hz), 127.01, 124.84, 122.15. 31 P NMR (121 MHz, Chloroform- d ) δ 18.35.HRMS (ESI) m / z [M + H]+ Calcd for C 19 H 13 Cl2NOPS + 403.9827; Found: 403.9831. Example 20 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-bromophenyl)phosphine oxide (2t) (3t): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-bromophenyl)phosphine oxide (2t) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 12 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 43%.

[0054] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 63.3mg, 43%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.09 (d, J = 7.4 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 7.74 (dd, J = 12.3, 8.3 Hz, 4H), 7.57 – 7.38 (m, 6H). 13 C NMR (75MHz, Chloroform- d ) δ 164.51 (d, J = 129.8 Hz), 154.22 (d, J = 21.8 Hz), 135.60, 132.53 (d, J = 10.5 Hz), 131.04 (d, J = 12.8 Hz), 129.28, 127.76, 127.18 (d, J =3.8 Hz), 125.89, 123.72, 121.10. 31 P NMR (121 MHz, Chloroform- d) δ 18.51. HRMS(ESI) m / z [M + H] + Calcd for C 19 H 13 Br2NOPS + 491.8817; Found: 491.8819. Example 21 Synthesized from 2-iodophenyl isothiocyanate (1a) and bis(4-(trifluoromethyl)phenyl)phosphine (2u) as raw materials (3u): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of bis(4-(trifluoromethyl)phenyl)phosphine oxide (2u) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 12 h. The reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow solid with a yield of 46%.

[0055] Yellow solid; mp: 130.9 – 132.5 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 65.0mg, 46%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.17 – 8.03 (m, 5H),7.97 (d, J = 7.3 Hz, 1H), 7.70 (d, J = 5.7 Hz, 4H), 7.55 – 7.43 (m, 2H). 13 C NMR (75 MHz, Chloroform- d ) δ 163.64 (d, J = 131.3 Hz), 154.21 (d, J = 22.5 Hz),135.71, 134.47, 133.56 (dq, J = 29.3, 3 Hz), 133.10, 131.25 (d, J = 10.5 Hz), 126.11 (d, J = 4.5 Hz), 124.84 – 124.48 (m), 123.91, 122.70 (q,J = 271.5 Hz), 121.19. 19 F NMR (282 MHz, Chloroform- d ) δ -63.31. 31 P NMR (121 MHz, Chloroform- d ) δ 16.51. HRMS (ESI) m / z [M + H] + Calcd for C 21 H 13 F6NOPS + 472.0354; Found: 472.0355. Example 22 Synthesized from 2-iodophenyl isothiocyanate (1a) and cyclic 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (2v) (3v): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (2v) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a yellow solid with a yield of 67%.

[0056] Yellow solid; mp: 126.3 – 127.7 ℃. R f = 0.5 (ethyl acetate / n-hexane= 1:1); 70.2mg, 67%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.18 – 7.87 (m, 5H), 7.80 – 7.71 (m, 1H), 7.56 – 7.27 (m, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ155.04, 154.69, 149.18 (d, J = 8.3 Hz), 136.83, 136.49 (d, J = 6.8 Hz), 134.21(d, J= 2.3 Hz), 131.64 (d, J = 11.3 Hz), 130.78, 128.73 (d, J = 15.0 Hz), 127.09(d, J = 21.0 Hz), 125.12 (t, J = 4.5 Hz), 123.89, 123.78, 123.61, 122.08, 121.82,121.61, 120.64, 120.63. 31 P NMR (121 MHz, Chloroform- d ) δ 13.98. HRMS (ESI) m / z :[M + H] + Calcd for C 19 H 13 NO2PS + 350.0399; Found: 350.0403. Example 23 Synthesized using 2-iodophenyl isothiocyanate (1a) and ethyl phenylphosphonite (2w) as raw materials (3w): 0.3 mmol of 2-iodophenyl isothiocyanate (1a) and 0.36 mmol of ethyl phenylphosphonite (2w) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 90%.

[0057] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 81.8mg, 90%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.21 (d, J = 7.2 Hz, 1H), 8.13 – 7.94(m, 2H), 7.64 – 7.50 (m, 2H), 7.55 – 7.43 (m, 2H), 4.44 – 4.18 (m, 1H), 1.44(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, Chloroform- d ) δ 164.10 (d, J = 165.8 Hz), 154.99 (d, J = 24.0 Hz), 136.82, 133.20 (d, J = 3.0 Hz), 132.21 (d, J = 10.5 Hz), 129.09 (d, J = 148.5 Hz), 128.68 (d, J = 14.3 Hz), 126.92, 126.76, 124.94,121.97, 62.93 (d, J = 6.8 Hz), 16.54 (d, J = 6.8 Hz). 31 P NMR (121 MHz, Chloroform- d ) δ 20.73. HRMS (ESI) m / z [M + H] + Calcd for C 15 H 15 NO2PS + 304.0556; Found: 304.0559. Example 24 Synthesized from 2-iodo-4-methyl-phenyl isothiocyanate (1b) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-4-methyl-phenyl isothiocyanate (1b) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 99%.

[0058] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);84.7mg, 99%. 1 H NMR (300 MHz, Chloroform- d ) δ 7.95 (s, 1H), 7.79 (d,J = 8.3 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 4.37 – 4.11 (m, 4H), 2.45 (s, 3H), 1.31 (t, J =7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 159.82 (d, J = 237.8 Hz), 155.10(d, J = 28.5 Hz), 137.06, 133.47, 128.82, 124.59, 121.37 (d, J = 1.5 Hz), 64.11(d, J = 6 Hz), 21.53, 16.31 (d, J = 6.8 Hz). 31 P NMR (121 MHz, Chloroform- d δ4.23. HRMS (ESI) m / z [M + H] + Calcd for C 12 H 17 NO3PS + 286.0661; Found: 286.0665. Example 25 Synthesized from 2-iodo-5-methyl-phenyl isothiocyanate (1c) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-5-methyl-phenyl isothiocyanate (1c) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 99%.

[0059] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);84.7mg, 99%. 1 H NMR (300 MHz, Chloroform-d ) δ 8.03 (d, J = 8.5 Hz, 1H), 7.70 (s,1H), 7.30 (dd, J = 8.5, 1.7 Hz, 1H), 4.34 – 4.13 (m, 4H), 2.44 (s, 3H), 1.31(t, J = 7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 158.57 (d, J = 237.8 Hz), 152.81 (d, J = 28.5 Hz), 137.53, 136.68 (d, J = 1.5 Hz), 128.69, 124.31, 121.53(d, J = 2.3 Hz), 64.54 (d, J = 6.0 Hz), 21.65, 16,30 (d, J = 6.0 Hz). 31 P NMR (121MHz, Chloroform- d δ 4.35. HRMS (ESI) m / z [M + H] + Calcd for C 12 H 17 NO3PS + 286.0661; Found: 286.0665. Example 26 Synthesized from 2-iodo-3-methyl-phenyl isothiocyanate (1d) and diethyl phosphite (2b): (4c) 0.3 mmol of 2-iodo-3-methyl-phenyl isothiocyanate (1d) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 86%.

[0060] Pale yellow, oily liquid. R f= 0.5 (ethyl acetate / n-hexane = 1:1); 73.5mg, 86%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.00 (d, J = 8.2 Hz, 1H), 7.41 (t, J =7.7 Hz, 1H), 7.24 (s, 1H), 4.25 (h, J = 7.2 Hz, 4H), 2.54 (s, 3H), 1.32 (t, J =7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 158.32 (d, J = 237.8 Hz), 153.41(d, J = 27.8 Hz), 136.04, 131.07 (d, J = 1.5 Hz), 126.11 (d, J = 2.3 Hz), 125.93,121.30, 62.97 (d, J = 6.0 Hz), 20.41, 15.30 (d, J = 6.8 Hz). 31 P NMR (121 MHz, Chloroform- d 4.22. HRMS (ESI) m / z [M + H] + Calcd for C 12 H 17 NO3PS + 286.0661; Found: 286.0663. Example 27 Synthesized using 2-iodo-4,5-dimethyl-phenyl isothiocyanate (1e) and diethyl phosphite (2b) as raw materials (4d): 0.3 mmol of 2-iodo-4,5-dimethyl-phenyl isothiocyanate (1e) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 99%.

[0061] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 88.8mg, 99%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.00 (s, 1H), 7.74 (s, 1H), 4.43 –4.19 (m, 4H), 2.42 (s, 6H), 1.39 (t, J = 7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 158.30 (d, J = 238.5 Hz), 153.55 (d, J = 28.5 Hz), 137.06,136.45, 134.11 (d, J = 1.5 Hz), 124.72, 121.60 (d, J = 1.5 Hz), 64.01 (d, J = 6.0Hz), 20.42 (d, J = 7.5 Hz), 16.33 (d, J = 6.0 Hz). 31 P NMR (121 MHz, Chloroform- d δ 4.58. HRMS (ESI) m / z [M + H] + Calcd for C 13 H 19 NO3PS + 300.0818; Found: 300.0820. Example 28 Synthesized from 2-iodo-4-methoxy-phenyl isothiocyanate (1f) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-4-methoxy-phenyl isothiocyanate (1f) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 98%.

[0062] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 88.5mg, 98%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.11 (d, J = 9.0 Hz, 1H), 7.41 (d, J =2.5 Hz, 1H), 7.18 (dd, J = 9.1, 2.5 Hz, 1H), 4.41 – 4.23 (m, 4H), 3.91 (s, 3H), 1.40 (t, J = 7.4 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 158.72 (d, J = 66.0 Hz), 155.11, 149.22 (d, J = 28.5 Hz), 138.24 (d, J = 2.3 Hz), 125.40, 117.31, 103.18(d, J = 2.3 Hz), 63.92 (d, J = 6.0 Hz), 55.80, 16.33 (d, J = 6.0 Hz). 31 P NMR (121MHz, Chloroform- d δ 4.33. HRMS (ESI) m / z [M + H] + Calcd for C 12 H 17 NO4PS +302.0610; Found: 302.0614. Example 29 Synthesized from 2-iodo-4-fluoro-phenyl isothiocyanate (1g) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-4-fluoro-phenyl isothiocyanate (1 g) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 89%.

[0063] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 77.2mg, 89%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.12 (dd, J = 9.1, 4.8 Hz, 1H), 7.60(dd, J = 8.0, 2.5 Hz, 1H), 7.25 (td, J = 8.9, 2.5 Hz, 1H), 4.33 – 4.19 (m, 4H), 1.35 – 1.30 (m, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 162.39 (d, J = 121.5 Hz), 159.10 (d, J = 112.5 Hz), 151.31 (d, J = 29.3 Hz), 137.62 (d, J = 13.5 Hz), 126.10(d, J = 9.8 Hz), 116.08 (d, J = 24.8 Hz), 107.85 (d, J = 28.5 Hz), 64.21 (d, J = 6.0Hz), 16.32 (d, J = 6.8 Hz). 19F NMR (282 MHz, Chloroform- d ) δ -112.62. 31 P NMR (121 MHz, Chloroform- d 3.43. HRMS (ESI) m / z [M + H] + Calcd for C 11 H 14 FNO3PS + 290.0411; Found: 290.0414. Example 30 Synthesized (4g) from 2-iodo-4-chloro-phenyl isothiocyanate (1h) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-4-chloro-phenyl isothiocyanate (1 h) and 0.36 mmol of diethyl phosphite (2 b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 88%.

[0064] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 80.5mg, 88%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.06 (d, J = 8.8 Hz, 1H), 7.91 (d, J =2.0 Hz, 1H), 7.45 (dd, J = 8.8, 2.1 Hz, 1H), 4.33 – 4.18 (m, 4H), 1.32 (t, J =7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 160.70 (d, J = 237.0 Hz), 153.07(d, J = 28.5 Hz), 137.51 (d, J= 1.5 Hz), 133.30, 127.94, 125.61, 121.50 (d, J =1.5 Hz), 64.16 (d, J = 6.0 Hz), 16.34 (d, J = 6.0 Hz). 31 P NMR (121 MHz, Chloroform- d 3.43. HRMS (ESI) m / z [M + H] + Calcd for C 11 H 14 ClNO3PS + 306.0115; Found: 306.0118. Example 31 Synthesized using 2-iodo-4-bromo-phenyl isothiocyanate (1i) and diethyl phosphite (2b) as starting materials (4h): 0.3 mmol of 2-iodo-4-bromo-phenyl isothiocyanate (1i) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product as a pale yellow oily liquid with a yield of 87%.

[0065] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 91.1mg, 87%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.16 (d, J = 1.9 Hz, 1H), 8.09 (d, J =8.8 Hz, 1H), 7.68 (dd, J = 8.8, 1.9 Hz, 1H), 4.41 – 4.28 (m, 4H), 1.41 (t, J =7.1 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 160.84 (d, J= 236.3 Hz), 153.37(d, J = 28.5 Hz), 138.01, 130.50, 125.86, 124.45 (d, J = 1.5 Hz), 121.21, 64.33(d, J = 6.0 Hz), 16.30 (d, J = 6.0 Hz). 31 P NMR (121 MHz, Chloroform- d ) δ 3.33.HRMS (ESI) m / z [M + H] + Calcd for C 11 H 14 BrNO3PS + 349.9610; Found: 349.9611. Example 32 Synthesized from 2,4-diiodophenyl isothiocyanate (1j) and diethyl phosphite (2b): (4i) 0.3 mmol of 2,4-diiodophenyl isothiocyanate (1j) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 85%.

[0066] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1);101.2mg, 85%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.37 (d, J = 1.6 Hz, 1H), 7.97(d, J = 8.7 Hz, 1H), 7.85 (dd, J = 8.7, 1.7 Hz, 1H), 4.33 (dt, J = 14.4, 7.2 Hz, 4H), 1.41 (t, J = 7.1 Hz, 6H). 13C NMR (75 MHz, Chloroform- d ) δ 160.69 (d, J =236.3 Hz), 153.82 (d, J = 28.5 Hz), 138.41 (d, J = 1.5 Hz), 136.12, 130.47 (d, J =1.5 Hz), 126.18, 92.25, 64.31 (d, J = 5.3 Hz), 16.33 (d, J = 6.0 Hz). 31 P NMR (121MHz, Chloroform- d 3.24. HRMS (ESI) m / z [M + H] + Calcd for C 11 H 14 INO3PS + 397.9471; Found: 397.9473. Example 33 Synthesized from 2-iodo-4-trifluoromethyl-phenyl isothiocyanate (1k) and diethyl phosphite (2b): 0.3 mmol of 2-iodo-4-trifluoromethyl-phenyl isothiocyanate (1k) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h, and the reaction was quenched with saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain a pure product as a pale yellow oily liquid with a yield of 89%.

[0067] Pale yellow, oily liquid. R f = 0.5 (ethyl acetate / n-hexane = 1:1); 90.5mg, 89%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.36 (d, J = 9.0 Hz, 2H), 7.82 (dd, J=8.7, 1.8 Hz, 1H), 4.44 – 4.30 (m, 4H), 1.46 – 1.40 (m, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 163.83 (d, J = 234.8 Hz), 156.21 (d, J = 27.8 Hz), 136.40 (d, J =1.5 Hz), 129.09 (q, J = 32.3 Hz), 125.47, 123.81 (d, J = 3.8 Hz), 120.23 (q, J =271.5 Hz), 119.85 (d, J = 3.0 Hz), 64.37 (d, J = 6.0 Hz), 16.27 (d, J = 6.0 Hz). 19 FNMR (282 MHz, Chloroform- d ) δ -61.71. 31 P NMR (121 MHz, Chloroform- d δ 2.85.HRMS (ESI) m / z [M + H] + Calcd for C 12 H 14 F3NO3PS + 340.0379; Found: 340.0382. Example 34 Synthesized using 2-iodo-naphthyl isothiocyanate (1l) and diethyl phosphite (2b) as raw materials (4k): 0.3 mmol of 2-iodo-naphthylphenyl isothiocyanate (1l) and 0.36 mmol of diethyl phosphite (2b) were added to a reaction flask, along with 2 equivalents of cesium carbonate. The reaction was carried out at 75 °C for 1 h. The reaction was quenched by adding saturated NH4Cl. The organic layer was washed three times with water and extracted three times with ethyl acetate. The organic phases were combined, dried, and separated by column chromatography to obtain the pure product, which was a pale yellow oily liquid with a yield of 99%.

[0068] Pale yellow, oily liquid. R f= 0.5 (ethyl acetate / n-hexane = 1:1);95.4mg, 99%. 1 H NMR (300 MHz, Chloroform- d ) δ 8.75 (s, 1H), 8.44 (s, 1H), 8.05(d, J = 9.4 Hz, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.60 – 7.49 (m, 2H), 4.48 – 4.27(m, 4H), 1.43 (t, J = 7.4 Hz, 6H). 13 C NMR (75 MHz, Chloroform- d ) δ 162.27 (d, J =235.5 Hz), 152.85 (d, J = 29.3 Hz), 134.30 (d, J = 1.5 Hz), 132.21 (d, J = 6.8 Hz), 128.93, 126.97 (d, J = 36.8 Hz), 126.00, 123.42, 120.61 (d, J = 1.5 Hz), 64.30(d, J = 6.0 Hz), 16.41 (d, J = 6.8 Hz). 31P NMR (121 MHz, Chloroform-d) δ 3.67.HRMS (ESI) m / z: [M + H]+ Calcd for C15H17NO3PS+ 322.0661; Found: 322.0662. The above description is merely an embodiment of the present invention and is not intended to limit the invention. Those skilled in the art can make various modifications to the technical solutions in the embodiments based on the above description. It is neither necessary nor possible to exhaustively describe all possible implementations. Any modifications, variations, substitutions, etc., made based on the technical content disclosed in this invention are equivalent to equivalent implementations and should be included within the protection scope of this invention.

Claims

1. A method for synthesizing 2-phosphobenzothiazole, characterized in that, The reaction was carried out using 2-iodoaryl isothiocyanate and H–P substrate as raw materials, cesium carbonate (Cs2CO3) as base and ester as solvent, at 60–90 °C. The reaction formula is as follows: In the reaction formula, R 1 The selection range includes: hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, or trifluoromethyl; R 2 R 3 Each group is independently selected from the following groups: C1-C6 alkoxy, C1-C6 alkyl, C3-C7 cycloalkyl, and optionally substituted aryl; the substituents of the optionally substituted aryl include halogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, and trifluoromethyl; or R 2 and R 3 Together with the phosphorus atoms to which they are attached, they form a 5- to 14-membered ring system selected from those having 1 phosphorus heteroatom and 0 to 2 oxygen heteroatoms, which may be either monocyclic or fused ring.

2. The method for synthesizing 2-phosphobenzothiazole according to claim 1, characterized in that, The synthesis method described herein involves the following steps: 2-iodoaryl isothiocyanate, H-P substrate, and cesium carbonate are added to a container, solvent is added, and the mixture is heated until the reactants are eliminated.

3. The method for synthesizing 2-phosphobenzothiazole according to claim 2, characterized in that, After the reaction is complete, saturated NH4Cl is added to quench the reaction.

4. The method for synthesizing 2-phosphobenzothiazole according to claim 3, characterized in that, The product was extracted with an ester solvent and then purified by column chromatography to obtain the target product, 2-phosphotenthiazole.

5. The method for synthesizing 2-phosphobenzothiazole according to claim 1, characterized in that, The molar ratio of the 2-iodoaryl isothiocyanate, H-P substrate, and cesium carbonate is 1:(1.1~1.3):(1.8~2.2).

6. The method for synthesizing 2-phosphobenzothiazole according to claim 1, characterized in that, 2-Iodoaryl isothiocyanates include 2-iodophenyl isothiocyanate, 2-iodo-4-methylphenyl isothiocyanate, 2-iodo-5-methylphenyl isothiocyanate, 2-iodo-3-methylphenyl isothiocyanate, 2-iodo-4,5-dimethylphenyl isothiocyanate, 2-iodo-4-methoxyphenyl isothiocyanate, 2-iodo-4-fluorophenyl isothiocyanate, 2-iodo-4-chlorophenyl isothiocyanate, 2-iodo-4-bromophenyl isothiocyanate, 2,4-diiodophenyl isothiocyanate, 2-iodo-4-trifluoromethylphenyl isothiocyanate, and 2-iodo-naphthyl isothiocyanate.

7. The method for synthesizing 2-phosphobenzothiazole according to claim 1, characterized in that, The HP substrate in R 2 and R 3 In the case where the phosphorus atoms to which they are attached are not cyclic, these include phosphite diesters, secondary phosphine oxides, and phosphite esters.

8. The method for synthesizing 2-phosphobenzothiazole according to claim 7, characterized in that, The phosphite diesters include dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, and di-n-butyl phosphite; secondary phosphine oxides include dimethylphosphine oxide, di-n-butylphosphine oxide, dicyclohexylphosphine oxide, diphenylphosphine oxide, bis(4-methylphenyl)phosphine oxide, bis(2-methylphenyl)phosphine oxide, bis(3,5-dimethylphenyl)phosphine oxide, bis(4-methoxyphenyl)phosphine oxide, bis(4-tert-butylphenyl)phosphine oxide, bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine oxide, bis(4-phenylphenyl)phosphine oxide, bis(4-fluorophenyl)phosphine oxide, bis(4-chlorophenyl)phosphine oxide, bis(4-bromophenyl)phosphine oxide, and bis(4-trifluoromethylphenyl)phosphine oxide; and phosphite esters, including ethyl phenylphosphite.

9. The method for synthesizing 2-phosphobenzothiazole according to claim 7, characterized in that, The HP substrate in R 2 and R 3 When cyclically formed with the phosphorus atoms to which they are attached, they include 5,5-dimethyl-1,3,2-dioxophosphacyclohexane-2-oxide and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide.

10. The method for synthesizing 2-phosphobenzothiazole according to claim 1, characterized in that, Ethyl acetate is used as the solvent.

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