Method for constructing imino thiazole derivative by using alkali to promote denitrification of 1, 2, 3-triazole

Abstract

The invention discloses a method for constructing an imino thiazole derivative by using alkali to promote nitrogen removal of 1, 2, 3-triazole, which comprises the following steps: reacting a 1, 4-disubstituted-1, 2, 3-triazole derivative and isothiocyanate as raw materials in the presence of alkali and a solvent at 10-120 DEG C, and performing extraction, concentration and column chromatography separation and purification on the reaction product to obtain the imino thiazole derivative. According to the method, raw materials are easy to obtain, transition metal does not need to participate, operation is easy and convenient, and a convenient and efficient new method can be provided for synthesis of thiazole drugs, pesticides and organic materials.

Description

Technical Field

[0001] The invention relates to a method for constructing an iminothiazole derivative by promoting the denitrogenation of 1,2,3-triazole with a base, and belongs to the technical field of medicine, pesticide and material intermediates and organic synthesis. Background Art

[0002] Iminothiazole contains both thiazole and imine structures and is an important class of heterocyclic compounds, especially widely used in the fields of medicine and pesticides. It has many important biological activities such as anti-inflammatory, antibacterial, anticancer, anti-leishmanial, antimicrobial, herbicidal, and anti-HIV (Med.Chem.Res.2012,21,2123; Molecules 2022,27,3994). It can also be used as a platelet GPIIB / IIIA receptor antagonist, alkaline phosphatase inhibitor, neurodegenerative drug polyvinyl fluoride-α analogue and skin whitening agent (J.Enzyme Inhib.Med.Chem.2023,38,2163394.).

[0003] Therefore, this unique heterocyclic compound has attracted much attention due to its multiple biological activities and wide applications in organic and medicinal chemistry, and the synthesis methods are endless. Safari et al. used substituted thiourea and α-halogenated carbonyl compounds as raw materials based on the Hantzsch method, and synthesized iminothiazole derivatives under the catalysis of chitosan nanomaterials. The reaction conditions are relatively simple, but the reaction conditions need to be strictly controlled (Catal Commun. 2016, 77, 108.); Periakaruppan used the condensation of 2-amino-1,3-thiazoline with aldehyde to control the selectivity of the product, but the reaction requires special substrates and has certain restrictions on the compatibility of functional groups (Tetrahedron Lett. 2017, 58, 3057); Shahvelayati et al. used a multi-component reaction of isothiocyanate, amino acid and α-halogenated ketone to synthesize the target compound, and the reaction used an ionic liquid as a solvent (Chin. Chem. Lett. 2014, 25, 119-122). The above synthesis methods are inevitably subject to unfavorable factors such as difficult preparation of raw materials, harsh reaction conditions, and complex synthesis systems. Summary of the invention

[0004] In view of the problems existing in the traditional method for synthesizing iminothiazole and its derivatives, the present invention provides a method for constructing iminothiazole by denitrogenation of 1,2,3-triazole promoted by base. The method of the present invention adopts 1,2,3-triazole derivatives and isothiocyanate as synthesis precursors, and obtains iminothiazole derivatives under the promotion of base. The raw materials are easy to obtain, the reaction is simple, the cost is low, the post-treatment is simple, and it is easy to expand industrial production.

[0005] The method for constructing an iminothiazole derivative by promoting the denitrogenation of 1,2,3-triazole with a base is as follows: 1,4-disubstituted-1,2,3-triazole derivative, a base, a solvent and an isothiocyanate are added into a reactor, reacted at 10 to 120° C. for 3 to 11 hours, and the product is extracted, concentrated and purified by column chromatography to obtain an iminothiazole derivative.

[0006] The structural formula of the iminothiazole derivative is as follows:

[0007]

[0008] Among them, R 1 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, monohalogenated phenyl and polyhalogenated phenyl; R 2 is one of phenyl, heteroaryl, alkyl-substituted phenyl, and halogenated phenyl; R 3 It is one of phenyl, heteroaryl and substituted phenyl.

[0009] The structural formula of the 1,4-disubstituted-1,2,3-triazole derivative is as follows:

[0010]

[0011] Among them, R 1 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, monohalogenated phenyl and polyhalogenated phenyl; R 2 It is one of phenyl, heteroaryl, alkyl-substituted phenyl and halogenated phenyl.

[0012] The isothiocyanate structural formula is as follows:

[0013]

[0014] Among them, R 3 It is one of phenyl, heteroaryl and substituted phenyl.

[0015] The molar ratio of the 1,4-disubstituted-1,2,3-triazole to the base is 1:(1-3), the molar ratio of the 1,4-disubstituted-1,2,3-triazole to the solvent is 1:(20-80), and the molar ratio of the 1,4-disubstituted-1,2,3-triazole to the isothiocyanate is 1:(1-4).

[0016] The base is potassium tert-butoxide ( t BuOK), sodium hydride (NaH), potassium amide (KNH2), n-butyl lithium ( n BuLi), potassium carbonate, cesium carbonate, and potassium phosphate.

[0017] The solvent is one of benzene, dichloromethane (DCM), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), and N,N-dimethylacetamide (DMA).

[0018] Compared with the prior art, the present invention has the following advantages:

[0019] 1,4-disubstituted-1,2,3-triazole is used as the raw material for synthesizing the target compound, and reacts with isothiocyanate under the action of base to efficiently obtain the target product; the reaction does not require the participation of transition metals, which is in line with the concept of green development, has simple post-processing, and is easy to expand production, which can provide a convenient and efficient new method for the synthesis of thiazole drugs, pesticides and organic materials. DETAILED DESCRIPTION

[0020] The present invention is further described in detail below in conjunction with embodiments, but the protection scope of the present invention is not limited to the described contents.

[0021] Example 1: Synthesis of 2-phenylimino-1,-4-diphenylthiazole (3a)

[0022] 1,4-Diphenyl-1,2,3-triazole (1a, 1 mmol), phenylisothiocyanate (2a, 4 mmol), potassium tert-butoxide (1 mmol), and THF (20 mmol) were added to a 10 mL reactor equipped with a stirrer, reacted at 10°C for 3 hours, diluted with 40 mL of deionized water, and extracted with 150 mL of ethyl acetate three times, the ethyl acetate extracts were collected and combined, the extracts were dried, and the solvent was evaporated under reduced pressure to obtain a crude product, and the crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 114.8 mg of 2-phenylimino-1,4-diphenylthiazole (3a), with a yield of 35%;

[0023] The reaction equation is as follows:

[0024]

[0025] The NMR data of compound 3a are as follows:

[0026] 1 H NMR (600MHz, CDCl3) δ7.60 (d, J = 7.7Hz, 2H), 7.43 (t, J = 7.8Hz, 2H), 7.32 (t, J = 7.0Hz, 2H), 7.30-7.23 (m, 5H), 7.21-7.15 (m, 1H), 7.10-7.02 (m, 4H). 13C NMR (151MHz, CDCl3) δ156.8,151.8,138.6,131.5,129.6,129.3,128.9,127.4,127.2,125.3,124.6,123.6,122.7,121.6,116.0.

[0027] Example 2: Synthesis of 2-phenylimino-1-phenyl-4-p-tolylthiazole (3b)

[0028] 1-Phenyl-4-p-methylphenyl-1,2,3-triazole (1b, 1 mmol), phenylisothiocyanate (2a, 4 mmol), cesium carbonate (2 mmol), and THF (25 mmol) were added to a 10 mL reactor equipped with a stirrer, reacted at 20°C for 3 hours, diluted with 40 mL of deionized water, and extracted with 150 mL of ethyl acetate three times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 174 mg of 2-phenylimino-1-phenyl-4-p-tolylthiazole (3b), with a yield of 51%;

[0029] The reaction equation is as follows:

[0030]

[0031] The NMR data of compound 3b are as follows:

[0032] 1 H NMR (500MHz, CDCl3) δ7.65-7.60(m,2H),7.45(t,J=8.0Hz,2H),7.35-7.27(m,3H),7. 21-7.16(m,2H),7.10(d,J=8.0Hz,2H),7.08-7.03(m,3H),7.02(s,1H),2.30(s,3H). 13 C NMR (126MHz, CDCl3) δ156.7,152.0,139.0,137.4,129.7,129.6,129.3,128.9,127.1,125.3,124.7,123.5,122.0,121.6,116.4,21.2.

[0033] Example 3: Synthesis of 2-phenylimino-1-p-tolyl-4-m-tolylthiazole (3c)

[0034] 1-p-methylphenyl-4-m-methylphenyl-1,2,3-triazole (1c, 1mmol), phenylisothiocyanate (2a, 3mmol), potassium tert-butoxide (3mmol), and THF (30mmol) were added to a 10mL reactor equipped with a stirrer and reacted at 30°C for 4 hours; 40mL of deionized water was added for dilution and then extracted with 150mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 163mg of 2-phenylimino-1-p-tolyl-4-m-tolylthiazole (3c), with a yield of 46%;

[0035] The reaction equation is as follows:

[0036]

[0037] The NMR data of compound 3c are as follows:

[0038] 1 H NMR (600MHz, CDCl3) δ7.54(d,J=8.1Hz,2H),7.36(t,J=7.7Hz,2H),7.29(d,J=8.0Hz,2H), 7.22(t,J=7.6Hz,1H),7.13(d,J=7.7Hz,2H),7.11-7.03(m,5H),2.40(s,3H),2.34(s,3H). 13 C NMR (151MHz, CDCl3) δ157.2,152.1,138.7,137.3,136.2,131.6,130.0,129.6 ,128.9,128.2,125.4,125.3,123.5,122.8,121.7,121.6,115.9,21.5,21.3.

[0039] Example 4: Synthesis of 2-phenylimino-1,4-di(p-tolyl)thiazole (3d)

[0040] 1,4-Di-p-methylphenyl-1,2,3-triazole (1d, 1 mmol), phenylisothiocyanate (2a, 3 mmol), sodium hydride (3 mmol), and DMA (35 mmol) were added to a 10 mL reactor equipped with a stirrer and reacted at 35°C for 5 hours; 40 mL of deionized water was added for dilution and then extracted with 150 mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents. The eluent was collected and dried by rotary evaporation at 45°C to obtain 156.9 mg of 2-phenylimino-1-p-tolyl-4-p-tolylthiazole (3d) with a yield of 44%.

[0041] The reaction equation is as follows:

[0042]

[0043] The NMR data of the compound are as follows:

[0044] 1 H NMR (600MHz, CDCl3) δ7.54(d,J=8.2Hz,2H),7.36(t,J=7.6Hz,3H),7.30(d,J=8.1Hz,2H),7.22(d, J=8.0Hz,2H),7.15(d,J=8.0Hz,2H),7.10(d,J=7.8Hz,3H),7.05(s,1H),2.41(s,3H),2.35(s,3H). 13 C NMR (126MHz, CDCl3) δ157.0,152.1,137.3,137.2,136.5,130.0,129.7,129.5,129.0,125.3,124.7,123.4,122.3,121.7,116.1,21.3,21.2.

[0045] Example 5: Synthesis of 2-phenylimino-1,4-di(o-tolyl)thiazole (3e)

[0046] 1,4-di-o-methylphenyl-1,2,3-triazole (1e, 1 mmol), phenylisothiocyanate (2a, 2 mmol), sodium hydride (2 mmol), and DMA (40 mmol) were added to a 10 mL reactor equipped with a stirrer in a molar ratio of 1:2:2:40, and reacted at 40°C for 5 hours; 40 mL of deionized water was added for dilution, and then extracted with 150 mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 185.4 mg of 2-phenylimino-1-o-tolyl-4-o-tolylthiazole (3e), with a yield of 52%;

[0047] The reaction equation is as follows:

[0048]

[0049] The NMR data of compound 3e are as follows:

[0050] 1 H NMR (500MHz, CDCl3) δ7.45-7.42(m,1H),7.40-7.37(m,1H),7.37-7.30(m,5H) ,7.25-7.17(m,3H),7.09-7.03(m,3H),6.64(s,1H),2.46(s,3H),2.44(s,3H). 13 C NMR (126MHz, CDCl3) δ157.4,152.2,138.0,136.4,136.1,131.5,131.1,129.6,129.4 ,129.2,129.0,128.2,128.0,127.2,126.4,125.4,123.3,121.7,114.8,21.5,18.3.

[0051] Example 6: Synthesis of 2-phenylimino-1-o-tolyl-4-p-tolylthiazole (3f)

[0052] 1-o-methylphenyl-4-p-methylphenyl-1,2,3-triazole (1f, 1 mmol), phenylisothiocyanate (2a, 2 mmol), n-butyllithium (1 mmol), and DMA (45 mmol) were added to a 10 mL reactor equipped with a stirrer and reacted at 45°C for 5 hours; 40 mL of deionized water was added for dilution and then extracted with 150 mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents. The eluent was collected and dried by rotary evaporation at 45°C to obtain 142.6 mg of 2-phenylimino-1-o-tolyl-4-p-tolylthiazole (3f) with a yield of 40%.

[0053] The reaction equation is as follows:

[0054]

[0055] The NMR data of 3f compound are as follows:

[0056] 1 H NMR (500MHz, CDCl3) δ7.43-7.39(m,1H),7.39-7.32(m,5H),7.22(d,J=8.2Hz,2H) ,7.14(d,J=8.1Hz,2H),7.09-7.04(m,3H),6.88(s,1H),2.41(s,3H),2.35(s,3H). 13 CNMR (126MHz, CDCl3) δ157.0,152.3,138.0,137.3,136.5,131.5,129.7,129. 5,129.1,129.0,128.1,127.2,124.6,123.4,122.4,121.7,116.0,21.2,18.3.

[0057] Example 7: Synthesis of 2-phenylimino-1-m-tolyl-4-p-tolylthiazole (3 g)

[0058] 1-m-methylphenyl-4-p-methylphenyl-1,2,3-triazole (1 g, 1 mmol), phenylisothiocyanate (2a, 1 mmol), n-butyllithium (2 mmol), and DMA (50 mmol) were added to a 10 mL reactor equipped with a stirrer, and reacted at 50°C for 5 hours; 40 mL of deionized water was added for dilution, and then 150 mL of ethyl acetate was used for extraction three times, and the ethyl acetate extracts were collected and combined, and the extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product, and the crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether: ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 181.8 mg of 2-phenylimino-1-m-tolyl-4-p-tolylthiazole (3 g), with a yield of 51%;

[0059] The reaction equation is as follows:

[0060]

[0061] The NMR data of 3g compound are as follows:

[0062] 1 H NMR (500MHz, CDCl3) δ7.49-7.44(m,2H),7.39-7.33(m,3H),7.22(d,J=8.2Hz,2H),7 .14(t,J=7.8Hz,3H),7.09(d,J=7.5Hz,3H),7.05(s,1H),2.43(s,3H),2.34(s,3H). 13 C NMR (126MHz, CDCl3) δ157.0,152.2,139.4,139.0,137.4,129.7,129.6,129.2 ,129.0,128.1,126.1,124.7,123.5,122.7,122.3,121.7,116.2,21.6,21.3.

[0063] Example 8: Synthesis of 2-phenylimino-1-m-tolyl-4-m-fluorophenylthiazole (3h)

[0064] 1-m-methylphenyl-4-m-fluorophenyl-1,2,3-triazole (1h, 1mmol), phenylisothiocyanate (2a, 1mmol), potassium tert-butoxide (2mmol), and DMF (25mmol) were added to a 10mL reactor equipped with a stirrer in a molar ratio of 1:1:2:55, and reacted at 55°C for 6 hours; 40mL of deionized water was added for dilution, and then extracted with 150mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 169.4mg of 2-phenylimino-1-m-tolyl-4-m-fluorophenylthiazole (3h), with a yield of 47%.

[0065] The reaction equation is as follows:

[0066]

[0067] The NMR data of compound 3h are as follows:

[0068] 1 H NMR(600MHz, CDCl3)δ7.49(d,J=8.2Hz,2H),7.34(t,J=7.8Hz,2H),7.29-7.22(m,3 H),7.10-7.02(m,5H),6.98(d,J=10.0Hz,1H),6.90(t,J=8.3Hz,1H),2.37(s,3H). 13 CNMR(151MHz, CDCl3)δ163.2(d,J=246.3Hz),156.7,151.9,137.5,135.9,133.9(d,J=8.4Hz),130.5(d,J=8.6Hz),130.0,1 29.6, 125.3, 124.0, 123.7, 121.5, 120.2 (d, J = 2.7Hz), 114.5 (d, J = 2.8Hz), 114.1 (d, J = 21.3Hz), 111.3 (d, J = 23.2Hz), 21.3.

[0069] Example 9: Synthesis of 2-phenylimino-1-m-tolyl-4-p-fluorophenylthiazole (3i)

[0070] 1-m-Methylphenyl-4-p-fluorophenyl-1,2,3-triazole (1i, 1 mmol), phenylisothiocyanate (2a, 4 mmol), potassium carbonate (2 mmol), and DMF (60 mmol) were added to a 10 mL reactor equipped with a stirrer and reacted at 60°C for 7 hours; 40 mL of deionized water was added for dilution and then extracted with 150 mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography using petroleum ether and ethyl acetate (volume ratio of petroleum ether:ethyl acetate is 1:10) as eluents. The eluent was collected and dried by rotary evaporation at 45°C to obtain 123.6 mg of 2-phenylimino-1-m-tolyl-4-p-fluorophenylthiazole (3i) with a yield of 35%.

[0071] The reaction equation is as follows:

[0072]

[0073] The NMR data of 3i compound are as follows:

[0074] 1 H NMR (600MHz, CDCl3) δ7.50 (d, J = 8.2Hz, 2H), 7.33 (t, J = 7.7Hz, 2H), 7.29-7.22 (m, 4H), 7.06 (t, J = 8.5Hz, 3H), 7.03-6.97 (m, 3H), 2.38 (s, 3H). 13 C NMR (151MHz, CDCl3) δ162.0 (d, J = 247.5Hz), 157.0, 152.0, 137.4, 136.1 130.0, 129.6, 127.9 (d, J = 3.3Hz), 126.3 (d, J = 8.0Hz), 125.3, 123.6, 122.8, 121.6, 116.0 (d, J = 22.0Hz), 114.8, 21.3.

[0075] Example 10: Synthesis of 2-phenylimino-1-m-tolyl-4-p-methoxyphenylthiazole (3j)

[0076] 1-m-methylphenyl-4-p-methoxyphenyl-1,2,3-triazole (1j, 1 mmol), phenylisothiocyanate (2a, 3 mmol), potassium carbonate (3 mmol), and DMF (20 mmol) were added to a 10 mL reactor equipped with a stirrer, and reacted at 65°C for 8 hours; 40 mL of deionized water was added for dilution, and then 150 mL of ethyl acetate was used for extraction three times, and the ethyl acetate extracts were collected and combined, and the extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product, and the crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (petroleum ether:ethyl acetate volume ratio of 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 178.5 mg of 2-phenylimino-1-m-tolyl-4-p-methoxyphenylthiazole (3j), with a yield of 48%;

[0077] The reaction equation is as follows:

[0078]

[0079] The NMR data of the compound are as follows:

[0080] 1 H NMR(600MHz, CDCl3)δ7.51(d,J=8.1Hz,2H),7.33(t,J=7.7Hz,2H),7.27(s,1H),7.25-7.2 1(m,3H),7.08-7.04(m,3H),6.94(s,1H),6.85(d,J=8.5Hz,2H),3.79(s,3H),2.38(s,3H). 13 C NMR (151MHz, CDCl3) δ159.1,157.3,152.2,137.2,136.3,130.0,129.6,126.0,125.3,124.4,123.4,121.7,121.6,115.7,114.4,55.5,21.3.

[0081] Example 11: Synthesis of 2-phenylimino-1-m-tolyl-4-thienylthiazole (3k)

[0082] 1-m-methylphenyl-4-thiophene-1,2,3-triazole (1k, 1 mmol), phenylisothiocyanate (2a, 2 mmol), n-butyl lithium (3 mmol), and DMF (30 mmol) were added to a 10 mL reactor equipped with a stirrer in a molar ratio of 1:2:3:30, and reacted at 70°C for 6 hours; 40 mL of deionized water was added for dilution, and then extracted with 150 mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 139.3 mg of 2-phenylimino-1-m-tolyl-4-thienylthiazole (3k), with a yield of 40%;

[0083] The reaction equation is as follows:

[0084]

[0085] The NMR data of 3k compound are as follows:

[0086] 1 H NMR (600MHz, CDCl3) δ7.49(d,J=8.2Hz,2H),7.33(t,J=7.8Hz,2H),7.27(d,J=8.0Hz,2H),7.1 3(d,J=5.0Hz,1H),7.09-7.03(m,3H),6.97-6.92(m,2H),6.86(d,J=3.4Hz,1H),2.38(s,3H). 13 C NMR (126MHz, CDCl3) δ156.5,151.9,137.4,136.2,134.5,130.0,129.6,127.7,125.3,123.8,123.6,123.0,121.6,110.1,21.2.

[0087] Example 12: Synthesis of 2-m-tolueneimino-1-p-tolyl-4-phenylthiazole (31)

[0088] 1-p-methylphenyl-4-phenyl-1,2,3-triazole (1l, 1mmol), m-methylphenyl isothiocyanate (2b, 1mmol), potassium phosphate (3mmol), and DMF (40mmol) were added to a 10mL reactor equipped with a stirrer, and reacted at 80°C for 7 hours; 40mL of deionized water was added for dilution, and then 150mL of ethyl acetate was used for extraction 3 times, and the ethyl acetate extracts were collected and combined, and the extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product, and the crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (petroleum ether: ethyl acetate volume ratio of 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 131.7mg of 2-m-toluylimino-1-p-tolyl-4-phenylthiazole (3l), with a yield of 37%;

[0089] The reaction equation is as follows:

[0090]

[0091] The NMR data of compound 3l are as follows:

[0092] 1 H NMR(500MHz, CDCl3) δ7.56(d,J=7.1Hz,2H),7.39-7.34(m,4H),7.32(d,J=7.8Hz,2H ),7.30-7.26(m,2H),7.12(s,1H),6.94(d,J=5.8Hz,3H),2.44(s,3H),2.39(s,3H). 13 C NMR (126MHz, CDCl3) δ156.7,152.0,139.3,137.2,136.4,131.9,129.9,129.4 ,129.0,127.3,125.3,124.7,124.3,122.9,122.4,118.4,115.9,21.6,21.2.

[0093] Example 13: Synthesis of 2-p-tolueneimino-1-p-tolyl-4-phenylthiazole (3m)

[0094] 1-p-methylphenyl-4-phenyl-1,2,3-triazole (1l, 1mmol), p-methylphenyl isothiocyanate (2c, 1mmol), potassium carbonate (1mmol), and DMF (50mmol) were added to a 10mL reactor equipped with a stirrer, and reacted at a temperature of 85°C for 8 hours; 40mL of deionized water was added for dilution, and then 150mL of ethyl acetate was used for extraction 3 times, and the ethyl acetate extracts were collected and combined, and the extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product, and the crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 73.2mg of 2-p-methylphenylimino-1-p-methylphenyl-4-phenylthiazole (3m), with a yield of 22%;

[0095] The reaction equation is as follows:

[0096]

[0097] The NMR data of 3m compound are as follows:

[0098] 1 H NMR(500MHz, CDCl3)δ7.51(d,J=6.8Hz,2H),7.32-7.29(m,4H),7.28(s,1H),7.25-7.19(m,2H) ,7.14(d,J=7.4Hz,2H),7.06(d,J=1.7Hz,1H),6.96(d,J=6.7Hz,2H),2.38(s,3H),2.32(s,3H). 13 C NMR (126MHz, CDCl3) δ156.8,149.6,137.2,136.5,132.9,132.0,130.2,130.0,129.0,127.3,125.4 124.7,123.0,121.4,115.9,21.2,21.1.

[0099] Example 14: Synthesis of 2-p-fluorophenylimino-1-p-tolyl-4-phenylthiazole (3n)

[0100] 1-p-Toluene-4-phenyl-1,2,3-triazole (1l, 1mmol), p-fluorophenyl isothiocyanate (2d, 3mmol), sodium hydride (1mmol), and DMF (40mmol) were added to a 10mL reactor equipped with a stirrer in a molar ratio of 1:3:1:40, and reacted at a temperature of 100°C for 10 hours; 40mL of deionized water was added for dilution, and then 150mL of ethyl acetate was used for extraction three times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, and petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) were used as eluents. The eluent was collected and dried by rotary evaporation at 45°C to obtain 161.9mg of 2-p-fluorophenylimino-1-p-tolyl-4-phenylthiazole (3n), and the yield was 45%;

[0101] The reaction equation is as follows:

[0102]

[0103] The NMR data of 3n compound are as follows:

[0104] 1 H NMR (500MHz, CDCl3) δ7.54(d,J=8.3Hz,2H),7.39-7.30(m,7H),7.30-7.25(m,1H),7.11(s,1H),7.06(d,J=2.2Hz,2H),7.05(s,1H),2.43(s,3H). 13 C NMR (126MHz, CDCl3) δ159.4 (d, J = 241.4Hz), 157.5, 148.2 (d, J = 2.6Hz), 137.4, 136.3, 131.8, 13 0.0,129.0,127.5,125.4,124.7,123.0,122.9(d,J=8.0Hz),116.3,116.0(d,J=12.1Hz),21.2.

[0105] Example 15: Synthesis of 2-p-nitrophenylimino-1-p-tolyl-4-phenylthiazole (3o)

[0106] 1-p-methylphenyl-4-phenyl-1,2,3-triazole (1l, 1mmol), p-nitrobenzene isothiocyanate (2e, 4mmol), cesium carbonate (3mmol), and DCM (30mmol) were added to a 10mL reactor equipped with a stirrer in a molar ratio of 1:4:3:30, and reacted at a temperature of 110°C for 11 hours; 40mL of deionized water was added for dilution, and then extracted with 150mL of ethyl acetate for 3 times, and the ethyl acetate extracts were collected and combined. The extracts were dried and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel (200-300 mesh) column chromatography, using petroleum ether and ethyl acetate (the volume ratio of petroleum ether:ethyl acetate was 1:10) as eluents, and the eluent was collected and dried by rotary evaporation at 45°C to obtain 196.3mg of 2-p-nitrophenylimino-1-p-tolyl-4-phenylthiazole (3o), with a yield of 53%;

[0107] The reaction equation is as follows:

[0108]

[0109] The NMR data of 3o compound are as follows:

[0110] 1 H NMR (500MHz, CDCl3) δ8.23-8.17(m,2H),7.48(d,J=8.3Hz,2H),7.39-7.26(m,7H),7.20-7.16(m,2H),7.13(s,1H),2.42(s,3H). 13 C NMR (126MHz, CDCl3) δ157.8,157.5,143.2,138.2,135.9,131.1,130.1,129.2,128.0,125.6,125.6,125.0,123.1,121.9,117.1,21.3.

Claims

1. A method for constructing iminothiazole derivatives by base-promoting denitrogenation of 1,2,3-triazole, characterized in that: Using 1,4-disubstituted-1,2,3-triazole derivatives and isothiocyanate as raw materials, reacting in the presence of a base and a solvent at 10-120° C., extracting, concentrating, and separating and purifying the reaction product by column chromatography to obtain an iminothiazole derivative; The structural formula of the 1,4-disubstituted-1,2,3-triazole derivative is: The structural formula of isothiocyanate is: The structural formula of the iminothiazole derivative is as follows: In the above structural formula, R 1 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, monohalogenated phenyl and polyhalogenated phenyl; R 2 is one of phenyl, heteroaryl, alkyl-substituted phenyl, and halogenated phenyl; R 3 It is one of phenyl, heteroaryl and substituted phenyl.

2. The method of claim 1 for constructing iminothiazole derivatives by base-promoted denitrogenation of 1,2,3-triazole, characterized in that: The molar ratio of 1,4-disubstituted-1,2,3-triazole to isothiocyanate is 1:(1-4), and the molar ratio of 1,4-disubstituted-1,2,3-triazole to base is 1:(1-3).

3. The method of claim 1 for constructing iminothiazole derivatives by base-promoted denitrogenation of 1,2,3-triazole, characterized in that: The solvent is selected from benzene, dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, and N,N-dimethylacetamide.

4. The method of claim 1 for constructing iminothiazole derivatives by base-promoted denitrogenation of 1,2,3-triazole, characterized in that: The base is one of potassium tert-butoxide, sodium hydride, potassium amide, n-butyl lithium, potassium carbonate, cesium carbonate, and potassium phosphate.

Images