Trifluoromethyl benzothiazole-containing tertiary alcohol derivative as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a trifluoromethyl-containing benzothiazole tertiary alcohol derivative as well as a preparation method and application thereof, the structural formula of the trifluoromethyl-containing benzothiazole tertiary alcohol derivative is shown in the specification, in the formula, R1 and R2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or R1 and R2 independently form a naphthalene ring with the substituted benzene ring. The trifluoromethyl benzothiazole-containing tertiary alcohol derivative provided by the invention has a relatively good antibacterial effect on one or more of rhizoctonia solani, fusarium moniliforme, fusarium graminearum, fusarium oxysporum and phytophthora parasitica var nicotianae. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and specifically relates to a tertiary alcohol derivative containing trifluoromethylbenzothiazole, and a preparation method and application thereof. Background Art

[0002] Benzothiazole is an important heterocyclic structure with abundant electrons on the ring. It is an important chemical and pharmaceutical intermediate. Its derivatives have diverse biological activities and have attracted extensive attention and in-depth research. These derivatives include antibacterial agents such as benzathiapiprolin and thiazopyralid. The structure of benzathiapiprolin is shown below:

[0003]

[0004] The results for thiazolin-ethyl are shown below:

[0005]

[0006] The above structures all contain benzothiazole structural units, but with the excessive use of antibacterial agents, some negative problems have also been brought about, such as the rampant diseases caused by drug resistance, which has gradually reduced the antibacterial effect of currently used antibacterial agents. In order to further meet the requirements for high antibacterial rates of antibacterial agents, new compounds need to be developed for the development of new antibacterial agents. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a trifluoromethylbenzothiazole tertiary alcohol derivative and a preparation method and application thereof, introduces the active substructure of benzothiazole into the trifluoromethyl tertiary alcohol skeleton structure, designs and synthesizes a series of novel benzothiazole compounds, which have good inhibitory effect on agricultural pathogens, are conducive to the further development of highly antibacterial antibacterial agents to meet the use requirements.

[0008] In addition, in the existing methods for developing antibacterial agents, the synthesis process all needs to use a catalyst, and the reaction conditions are harsh, which is not conducive to large-scale production applications. When developing new compounds, it is not only necessary to pay attention to the performance of the prepared compound, but also require that its synthesis method is simple and operable, so that it has the prospect of large-scale industrial production and application. For this reason, compounds with good performance and simple preparation methods also need to be further studied. The invention provides a preparation method of a trifluoromethylbenzothiazole tertiary alcohol derivative, in which no catalyst is used during the preparation process, the reaction conditions are mild, the process is simple, and it is easy to implement, which is very suitable for large-scale production applications. Simple method support is provided for further studying such derivatives.

[0009] The present invention is achieved through the following technical solutions.

[0010] The present invention provides a trifluoromethylbenzothiazole tertiary alcohol derivative, the structural formula of the trifluoromethylbenzothiazole tertiary alcohol derivative is:

[0011]

[0012] Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

[0013] Preferably, alkyl is methyl, alkoxy is methoxy, and halogen is fluorine, chlorine or bromine.

[0014] Preferably, R 1 R is selected from hydrogen, methyl, fluorine, chlorine, bromine or forms a naphthalene ring with a substituted benzene ring; 2 Selected from hydrogen, methoxy, chlorine, bromine or forming a naphthalene ring with a substituted benzene ring.

[0015] Preferably, the following compounds are used:

[0016]

[0017]

[0018]

[0019] The present invention provides a method for preparing the above-mentioned trifluoromethylbenzothiazole tertiary alcohol derivatives, comprising the following steps:

[0020] The trifluoromethylbenzothiazole tertiary alcohol derivatives shown in formula 3 are prepared by using the compounds of formula 1 and formula 2 as raw materials and cyclopentane as solvent through carbon-hydrogen bond functionalization.

[0021] Its synthetic route is as follows:

[0022]

[0023] Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

[0024] Preferably, the molar ratio of the compound of formula 1 to the compound of formula 2 is 1:1.

[0025] Preferably, the reaction is stirred at a temperature of 120° C. to 130° C. for 4 h to 13 h.

[0026] Preferably, the temperature is 120° C. and the reaction time is 8 h to 12 h.

[0027] Preferably, after the reaction is completed, the product can be purified by column chromatography. The post-treatment process is simple, and a high-yield product can be obtained by a simple preparation method.

[0028] The present invention provides the use of the above-mentioned trifluoromethylbenzothiazole tertiary alcohol derivatives or their pesticide acceptable salts in the preparation of agricultural antibacterial agents, wherein the agricultural antibacterial agent is used to inhibit one or more of Rhizoctonia solani, Fusarium moniliforme, Fusarium graminearum, Fusarium oxysporum and Nicotiana tabacum black leg pathogen.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] The present invention provides a tertiary alcohol derivative containing trifluoromethylbenzothiazole. It is found through detection that the synthesized compound has a good inhibitory effect on agricultural pathogens, can meet the current demand for improving the antibacterial effect of antibacterial agents, and is conducive to the further development of antibacterial agents with high antibacterial properties.

[0031] The present invention uses sulfolane as a solvent and introduces the active substructure of benzothiazole into the skeleton structure of trifluoromethyl tertiary alcohol by a simple method. No additional catalyst is needed during the reaction process, and only the raw materials need to be mixed, heated, stirred and reacted. The whole reaction is simple, highly operable, and very conducive to large-scale production and application, providing method support for further developing new agricultural antibacterial agents. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the high-resolution mass spectrum of compound 3ab.

[0033] Figure 2 This is the high-resolution mass spectrum of compound 3ac.

[0034] Figure 3 This is the high-resolution mass spectrum of compound 3ad.

[0035] Figure 4 This is the high-resolution mass spectrum of compound 3ae.

[0036] Figure 5 This is the high-resolution mass spectrum of compound 3af.

[0037] Figure 6 This is the high-resolution mass spectrum of compound 3ba.

[0038] Figure 7 This is the high-resolution mass spectrum of compound 3bb.

[0039] Figure 8 This is the high-resolution mass spectrum of compound 3bc.

[0040] Fig. 9 This is the high-resolution mass spectrum of compound 3be.

[0041] Fig.10 This is the high-resolution mass spectrum of compound 3bf.

[0042] Fig.11 This is the high-resolution mass spectrum of compound 3ca.

[0043] Fig.12 This is the high-resolution mass spectrum of compound 3cd.

[0044] Fig.13 This is the high-resolution mass spectrum of compound 3ce.

[0045] Fig.14 This is the high-resolution mass spectrum of compound 3cf.

[0046] Fig.15 This is the high-resolution mass spectrum of compound 3da.

[0047] Fig.16 This is the high-resolution mass spectrum of compound 3dc.

[0048] Fig.17 This is the high-resolution mass spectrum of compound 3dd.

[0049] Fig.18 This is the high-resolution mass spectrum of compound 3ea.

[0050] Fig.19 This is the high-resolution mass spectrum of compound 3ec.

[0051] Fig. 20 This is the high-resolution mass spectrum of compound 3ed.

[0052] Fig.21 This is the high-resolution mass spectrum of compound 3ef.

[0053] Fig. 22 This is the high-resolution mass spectrum of compound 3eg.

[0054] Fig.23 This is the high-resolution mass spectrum of compound 3eh.

[0055] Fig.24 This is the high-resolution mass spectrum of compound 3fa.

[0056] Fig.25 This is the high-resolution mass spectrum of compound 3ga.

[0057] Fig.26 This is the high-resolution mass spectrum of compound 3ha.

[0058] Fig. 27It is the chromatic crystal structure of compound 3ea. DETAILED DESCRIPTION

[0059] In order to enable those skilled in the art to better understand the technical solution of the present invention and implement it, the present invention is further described below in conjunction with specific embodiments and drawings, but the embodiments are not intended to limit the present invention. The experimental methods and detection methods described in the following embodiments are conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0060] The present invention provides a trifluoromethylbenzothiazole tertiary alcohol derivative, the structural formula of the trifluoromethylbenzothiazole tertiary alcohol derivative is shown in Formula 3:

[0061]

[0062] Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

[0063] Preferably, the alkyl group is methyl, the alkoxy group is methoxy, and the halogen group is fluorine, chlorine or bromine. 1 R is selected from hydrogen, methyl, fluorine, chlorine, bromine or forms a naphthalene ring with a substituted benzene ring; 2 Selected from hydrogen, methoxy, chlorine, bromine or forming a naphthalene ring with a substituted benzene ring.

[0064] The present invention provides a method for preparing a trifluoromethylbenzothiazole tertiary alcohol derivative, comprising the following steps:

[0065] The trifluoromethylbenzothiazole tertiary alcohol derivatives shown in formula 3 are prepared by reaction using the compounds of formula 1 and formula 2 as raw materials and cyclopentane as solvent.

[0066] Its synthetic route is as follows:

[0067]

[0068] Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

[0069] In a preferred embodiment of the present invention, the molar ratio of the compound of formula 1 to the compound of formula 2 is 1:1.

[0070] In a preferred embodiment of the present invention, the reaction is stirred at a temperature of 120° C. to 130° C. for 4 h to 13 h.

[0071] In a preferred embodiment of the present invention, the temperature is 120° C. and the reaction time is 8 h to 12 h.

[0072] In a preferred embodiment of the present invention, after the reaction is completed, column chromatography purification is performed. The present invention uses sulfolane as a solvent, introduces the benzothiazole active substructure into the trifluoromethyl tertiary alcohol skeleton structure by a simple method, does not require the use of an additional catalyst during the reaction, and only requires the raw materials to be mixed, heated, stirred and reacted. The entire reaction is simple, highly operable, and very conducive to large-scale production and application, providing method support for further development of new agricultural antibacterial agents.

[0073] The following content will be used to explain it in detail.

[0074] Test Example 1 to Test Example 16

[0075] The present invention uses the compound represented by Formula 1a and the compound represented by Formula 2b as raw materials, and prepares the product by changing the reaction conditions. The appropriate reaction conditions are screened by the yield. Test Examples 1 to 16 correspond to Groups 1 to 16 in Table 1. The specific screening conditions and yields are shown in Table 1. The synthesis route is as follows:

[0076]

[0077] Table 1 Reaction conditions screening

[0078]

[0079]

[0080] a Reaction conditions 1a (1.0 mmol), 2b (1.0 mmol), solvent (10 mL). b Liquid phase yield c No reaction d Isolated yield.

[0081] It can be seen from Table 1 that the reaction does not require the use of a catalyst, and a high yield product can be obtained when the reaction is stirred at 120°C to 130°C for 4h to 13h. Furthermore, the optimal reaction conditions are: compound 1a (1mmol) and compound 2b (1mmol) are mixed, cyclopentane (10mL) is used as a solvent, and stirred at 120°C for 12 hours. The obtained compound is purified by column chromatography to obtain the target compound 3ab.

[0082] Example 1 to Example 26

[0083] Under the above optimized reaction conditions, the reaction substrate was changed to obtain different products. Compound 1 (1 mmol) and compound 2 (1 mmol) were mixed, sulfolane (10 mL) was used as solvent, and stirred at 120°C for 12 hours. The obtained compound was purified by column chromatography to obtain the target compound 3. The reaction substrate and yield are shown in Table 2, and Examples 1 to 26 correspond to Groups 1 to 26 in Table 2.

[0084] The specific synthesis route is as follows:

[0085]

[0086] Table 2 Different reaction substrates and corresponding yields

[0087]

[0088]

[0089] The structural data of the above compounds are given below, and combined with Figure 1 to Figure 26 As shown:

[0090]

[0091] Compound 3ab.PE:EA=5:1,R f =0.43, yellow solid, mp: 158.3-159.8°C. 1 HNMR(400MHz,DMSO-d6)δ8.43(s,1H),7.98(dt,J=3.8,1.9Hz,2H),7.89-7.78(m,2H),7.66(dd,J=9.0,2.7Hz,1H), 7.47(dd,J=9.0,2.2Hz,1H),7.37(dtd,J=24.7,7.3,1.4Hz,2H),4.68(d,J=14.7Hz,1H),3.79(d,J=14.8Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.03,75.41(q,J=29.3Hz),118.39,119.89,122.45,122.73,124.50,125.38( q, J=288.8Hz),125.52,126.50,128.81,129.10,133.02,135.43,144.60,152.47,158.19,164.35ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.13ppm.HRMS(ESI):m / zcalcdforC 19 H 11ClF3NO3S[M+H] + 426.0179,found426.0175.

[0092]

[0093] Compound 3ac.PE:EA=5:1,R f =0.47, pale yellow solid, mp: 187.2-188.9℃. 1 HNMR (400MHz, DMSO-d6) δ8.42(s,1H),8.10(d,J=2.4Hz,1H),7.97(d,J=7.9Hz,1H),7. 88-7.72(m,3H),7.44-7.29(m,3H),4.68(d,J=14.7Hz,1H),3.79(d,J=14.8Hz,1H)ppm. 13 C NMR(101MHz,DMSO-d6)δ37.05,75.42(q,J=29.1Hz),116.93,118.64,120.39,122.44,122.73,124.46,125 .39(q,J=288.9Hz),125.51,126.49,131.80,135.43,135.78,144.52,152.47,152.89,158.14,164.36ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.12ppm.HRMS(ESI):m / z calcdfor C 19 H 11 BrF3NO3S[M+H] + 469.9673, found 469.9678.

[0094]

[0095] Compound 3ad.PE:EA=5:1,R f =0.4, pale yellow solid, mp: 167.1-168.9°C. 1 HNMR(400MHz,DMSO-d6)δ8.41(s,1H),7.98(d,J=7.6Hz,1H),7.84(d,J=8.0Hz,1H),7.78(s,1H) ,7.39(d,J=7.8Hz,1H),7.37-7.20(m,4H),4.71(d,J=14.7Hz,1H),3.90(s,3H),3.81(s,1H)ppm. 1313C NMR (101 MHz, DMSO-d6) δ 37.17, 56.57, 75.36 (q, J = 29.0 Hz), 115.48, 119.09, 120.74, 122.46, 122.74, 123.22, 125.30, 125.48 (q, J = 289.2 Hz), 125.50, 126.48, 135.48, 143.17, 145.99, 146.62, 152.45, 158.38, 164.47 ppm. 19 19F NMR (377 MHz, DMSO-d6) δ -77.31 ppm. HRMS (ESI): m / z calcd for C 20 H 14 F3NO4S [M-H] - 420.05174, found 420.04697.

[0096]

[0097] Compound 3ae. (PE:EA = 5:1, R f = 0.47, yellow-green solid, mp: 166.5 - 168.2 °C) 1 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.96 (d, J = 2.8 Hz, 2H), 7.85 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.65 (dd, J = 8.9, 2.6 Hz, 1H), 7.46 (d, J = 8.9 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.36 - 7.30 (m, 1H), 4.67 (d, J = 14.7 Hz, 1H), 3.79 (d, J = 14.8 Hz, 1H) ppm. 13 13C NMR (101 MHz, DMSO-d6) δ 37.12, 75.34 (q, J = 29.6 Hz), 118.27, 118.41, 119.88, 124.29, 124.37, 125.05, 125.33 (q, J = 288.6 Hz), 128.84, 129.13, 129.66, 133.08, 137.50, 144.68, 151.47, 152.48, 158.16, 165.60 ppm. 19 19F NMR (377 MHz, DMSO-d6) δ -77.11 ppm. HRMS (ESI): m / z calcd for C 19 H 11 ClF3NO3S [M+H] +426.0179, found 426.0183.

[0098]

[0099] Compound 3af.PE:EA=5:1,R f =0.33, white solid, mp: 212.1-213.9℃. 1 H NMR (400MHz, DMSO-d6) δ9.11(s,1H),8.40(d,J=8.5Hz,1H),8.23(d,J=9.1Hz,1H),8.04(d,J=8.1Hz,1H),7.94(d,J=7.2Hz,1H),7.84(d,J=15.8H z,1H),7.73(t,J=7.7Hz,1H),7.61(t,J=8.0Hz,2H),7.37(t,J=7.7Hz,1H),7.32-7.25(m,1H),4.78(d,J=14.7Hz,1H),3.85(d,J=14.7Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.19,75.75(q,J=29.1Hz),112.46,116.73,122.21,122.28,122.44,122.73,125.46,125.56(q,J =289.0Hz),126.45,126.86,129.00,129.32,129.54,130.39,135.03,135.50,140.93,152.43,154.01,158.74,164.57ppm. 19 FNMR(377MHz,DMSO-d6)δ-77.34ppm.HRMS(ESI):m / zcalcdforC 23 H 14 F3NO3S[MH] - 440.05682,found440.05161.

[0100]

[0101] Compound 3ba.PE:EA=5:1,R f =0.37, light yellow solid, mp: 157.5-159.1℃. 1H NMR (400MHz, DMSO-d6) δ8.46(s,1H),8.21(s,1H),7.90-7.70(m,3H),7.64-7.24(m,4H),4.72(d,J=14.8Hz,1H),3.81(d,J=14.8Hz,1H)ppm. 13 CNMR(101MHz,DMSO-d6)δ37.25,75.32(q,J=29.2Hz),116.29,118.23,118.52,122.93,124.22,124.96,125 .24,125.45(q,J=289.1Hz),129.55,129.77,133.42,137.53,145.84,151.44,153.85,158.65,165.70ppm. 19 FNMR(377MHz,DMSO-d6)δ-77.31ppm.HRMS(ESI):m / z calcd for C 19 H 11 BrF3NO3S[M+H] + 469.9673, found 469.9673.

[0102]

[0103] Compound 3bb.PE:EA=5:1,R f =0.5, yellow solid, mp: 185.6-186.9°C. 1 HNMR (400MHz, DMSO-d6) δ8.43(s,1H),8.22(d,J=2.1Hz,1H),7.94(t,J=3.0Hz,1H),7.88(s,1H),7.73(d,J=8.7H z,1H),7.60(ddd,J=9.1,4.9,2.6Hz,1H),7.53-7.39(m,2H),4.68(d,J=14.8Hz,1H),3.80(d,J=14.8Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.12,75.34(q,J=29.4Hz),118.24,118.33,119.87,124.23,125.33(q,J=289.1H z),124.35,124.97,128.79,129.10,129.58,132.97,137.50,144.70,151.46,152.47,158.16,165.57ppm. 19FNMR(377MHz,DMSO-d6)δ-77.14ppm.HRMS(ESI):m / z calcd for C 19 H 10 BrClF3NO3S[M+H] + 503.9284, found 503.9286.

[0104]

[0105] Compound 3bc.PE:EA=5:1,R f =0.48, yellow solid, mp: 182.1-184.3°C. 1 HNMR(400MHz,DMSO-d6)δ8.42(s,1H),8.21(s,1H),8.07(s,1H),7.87(s,1H),7.73(d,J=8.4Hz,2H ),7.48(d,J=7.0Hz,1H),7.37(d,J=9.0Hz,1H),4.68(d,J=14.8Hz,1H),3.79(d,J=14.8Hz,1H)ppm. 13 C NMR(101MHz,DMSO-d6)δ37.13,75.34(q,J=29.4Hz),116.91,118.24,118.59,120.36,124.23,124.30,124 .96,125.34(q,J=289.0Hz),129.57,131.78,135.74,137.49,144.63,151.46,152.88,158.12,165.57ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.14ppm.HRMS(ESI):m / zcalcdforC 19 H 10 Br2F3NO3S[M+H] + 547.8778,found547.8776.

[0106]

[0107] Compound 3be.PE:EA=5:1,R f =0.47, yellow solid, mp: 186.2-188.4°C. 1HNMR(400MHz,DMSO-d6)δ8.42(s,1H),8.27(d,J=2.0Hz,1H),7.98(d,J=2.6Hz,1H),7.87(s,1H),7.75(d,J=8.7Hz,1H),7.67(dd,J=8.9,2.6Hz,1H),7.54(dd,J=8.7,2.1Hz,1H),7.47(d,J=8.9Hz,1H),4.66(d,J=14.8Hz,1H),3.78(d,J=14.8Hz,1H)ppm. 13 C NMR(101MHz,DMSO-d6)δ37.12,75.34(q,J=29.2Hz),118.27,118.41,119.88,124.29,124.37,125.04,125.33(q,J=289.0Hz),128.83,129.13,129.65,133.07,137.50,144.68,151.47,152.48,158.16,165.60ppm. 19 FNMR(377MHz,DMSO-d6)δ-77.10ppm.HRMS(ESI):m / z calcd forC 19 H 10 BrClF3NO3S[M+H] + 503.9284,found 503.9286.

[0108]

[0109] Compound 3bf.PE:EA=5:1,R f =0.33, white solid, mp: 256.7 - 258.2 °C. 1 HNMR(400MHz,DMSO-d6)δ9.12(s,1H),8.40(d,J=8.5Hz,1H),8.22(d,J=9.1Hz,2H),8.04(d,J=8.1Hz,1H),7.90(s,1H),7.74(t,J=10.0Hz,1H),7.61(t,J=9.9Hz,1H),7.50(d,J=8.8Hz,1H),4.77(d,J=14.8Hz,1H),3.84(d,J=14.8Hz,1H)ppm. 13¹³C NMR (101 MHz, DMSO-d₆) δ 37.26, 75.66 (q, J = 29.2 Hz), 112.46, 116.72, 118.21, 122.04, 122.27, 124.27, 125.02, 125.51 (q, J = 288.9 Hz), 126.87, 129.00, 129.33, 129.54, 129.58, 130.39, 135.08, 137.56, 141.04, 151.42, 154.03, 158.71, 165.81 ppm. 19 ¹⁹F NMR (377 MHz, DMSO-d₆) δ -77.35 ppm. HRMS (ESI): m / z calcd for C 23 H 13 BrF₃NO₃S [M + H] + 519.9830, found 519.9830.

[0110]

[0111] Compound 3ca. PE:EA = 5:1, R f = 0.4, light yellow solid, mp: 184.5 - 186.3 °C. 1 ¹H NMR (400 MHz, DMSO-d₆) δ 8.46 (s, 1H), 8.00 (s, 1H), 7.91 (d, J = 8.5 Hz, 1H), 7.85 (s, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.40 (dd, J = 21.0, 8.1 Hz, 2H), 7.27 (t, J = 7.5 Hz, 1H), 4.75 (d, J = 14.6 Hz, 1H), 3.84 (d, J = 14.7 Hz, 1H) ppm. 13 ¹³C NMR (101 MHz, DMSO-d₆) δ 37.33, 75.36 (q, J = 29.3 Hz), 116.29, 118.54, 119.29, 122.90, 124.18, 125.12, 125.21, 125.45 (q, J = 288.8 Hz), 128.19, 129.76, 133.39, 134.73, 145.89, 153.66, 153.85, 158.67, 166.93 ppm. 19 ¹⁹F NMR (377 MHz, DMSO-d₆) δ -77.35 ppm. HRMS (ESI): m / z calcd for C 19 H 11 BrF₃NO₃S [M + H]+ 469.9673, found 469.9678.

[0112]

[0113] Compound 3cd.PE:EA=5:1,R f =0.28, light yellow solid, mp: 207.4-208.6℃. 1 HNMR (400MHz, DMSO-d6) δ8.42(s,1H),8.04(s,1H),7.94(d,J=8.5Hz,1H),7.83(s,1H),7.47(d,J=8.5Hz,1H ),7.33(d,J=7.4Hz,1H),7.29-7.18(m,2H),4.72(d,J=14.7Hz,1H),3.88(s,3H),3.81(d,J=14.7Hz,1H)ppm. 13 C NMR(101MHz,DMSO-d6)δ37.31,56.51,75.29(q,J=29.1Hz),115.42,119.07,119.33,120.72,123.00,124.29, 125.13, 125.26, 125.43 (q, J = 289.0Hz), 128.25, 134.75, 143.18, 146.16, 146.59, 153.64, 158.37, 166.91ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.35ppm.HRMS(ESI):m / z calcd for C 20 H 13 BrF3NO4S[M+H] + 499.9779, found 499.9782.

[0114]

[0115] Compound 3ce.PE:EA=5:1,R f =0.5, light yellow solid, mp: 176.6-177.5℃. 1 H NMR (400MHz, DMSO-d6) δ8.43(s,1H),8.02(s,1H),7.98-7.92(m,2H),7.88(s,1H),7.63(d,J= 8.9Hz,1H),7.47(dd,J=12.7,8.6Hz,2H),4.69(d,J=14.8Hz,1H),3.81(d,J=14.9Hz,1H)ppm.13 CNMR(101MHz,DMSO-d6)δ37.20,75.36(q,J=29.4Hz),118.39,119.34,119.87,124.29,125.14,125.33 (q,J=289.0Hz),128.28,128.82,129.12,133.04,134.71,144.75,152.49,153.68,158.16,166.81ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.15ppm.HRMS(ESI):m / zcalcd for C 19 H 10 BrClF3NO3S[M+H] + 503.9284, found 503.9285.

[0116]

[0117] Compound 3cf.PE:EA=5:1,R f =0.43, light yellow solid, mp: 186.5-187.8℃. 1 H NMR (400MHz, DMSO-d6) δ9.12(s,1H),8.39(d,J=8.4Hz,1H),8.20(d,J=9.0Hz,1H),8.01(d,J=9.9Hz,2H),7.90(d,J=9.5Hz, 2H),7.72(t,J=7.8Hz,1H),7.59(t,J=9.4Hz,2H),7.43(d,J=8.6Hz,1H),4.79(d,J=14.7Hz,1H),3.87(d,J=14.8Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.33,75.68(q,J=29.5Hz),112.45,116.70,119.28,121.98,122.24,124.27,125.14,125.51(q,J =289.1Hz),126.43,128.21,128.98,129.28,129.50,130.36,134.77,135.04,141.08,153.64,154.02,158.71,167.02ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.38ppm.HRMS(ESI):m / zcalcd for C 23 H 13BrF3NO3S[M+H] + 519.9830, found 519.9828.

[0118]

[0119] Compound 3da.PE:EA=5:1,R f =0.47, yellow-green solid, mp: 175.7-177.2°C. 1 HNMR(400MHz, DMSO-d6)δ8.46(s,1H),8.01(d,J=8.5Hz,1H),7.90(d,J=2.0Hz,1H),7.87-7.77( m,2H),7.70-7.55(m,1H),7.46-7.28(m,3H),4.72(d,J=14.7Hz,1H),3.82(d,J=14.8Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.35,75.33(q,J=29.2Hz),116.35,118.53,122.17,122.88,123.97,125.31,125.44(q,J =289.1Hz),125.64,129.75,129.82,131.31,133.52,133.59,134.29,145.89,153.31,153.86,158.65,167.16ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.31ppm.HRMS(ESI):m / zcalcd forC 19 H 11 ClF3NO3S[M+H] + 426.0179, found 426.0184.

[0120]

[0121] Compound 3dc.PE:EA=5:1,R f =0.48, white solid, mp: 164.5-166.1℃. 1 HNMR(400MHz,DMSO-d6)δ8.45(d,J=7.3Hz,1H),8.07-7.92(m,2H),7.91-7.77(m,2H),7 .67-7.54(m,1H),7.50-7.21(m,1H),4.70(d,J=14.7Hz,1H),3.82(d,J=14.8Hz,1H)ppm. 13C NMR (101MHz, DMSO-d6) δ37.21,75.35(q,J=29.6Hz),116.32,118.34,122.16,123.92,125.60,125.62,127.53(q,J =455.7Hz),128.79,129.10,131.31,132.98,134.25,144.78,152.47,153.32,153.85,158.17,158.64,167.01ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.34,-77.18ppm.HRMS(ESI):m / zcalcdfor C 19 H 10 BrClF3NO3S[M+H] + 503.9284, found 503.9288.

[0122]

[0123] Compound 3dd.PE:EA=5:1,R f =0.47, light yellow solid, mp: 198.6-200.3℃. 1 HNMR (400MHz, DMSO-d6) δ8.42(s,1H),8.02(d,J=8.6Hz,1H),7.92(d,J=2.0Hz,1H),7.84(s,1H),7.42-7. 31(m,2H),7.27(dt,J=15.6,8.3Hz,2H),4.71(d,J=14.7Hz,1H),3.89(s,3H),3.80(d,J=14.8Hz,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ37.33, 56.54, 75.27 (q, J = 29.3Hz)., 115.49, 119.07, 120.75, 122.19, 122.99, 124.01, 125.31, 125.50 (q, J = 288.8Hz), 125.66, 131.31, 134.30, 143.17, 146.17, 146.60, 153.29, 158.36, 167.13ppm. 19 FNMR(377MHz,DMSO-d6)δ-77.36ppm.HRMS(ESI):m / z calcd for C 20 H 13 ClF3NO4S[M+H] +456.0284, found 456.0285.

[0124]

[0125] Compound 3ea.PE:EA=5:1,R f =0.38, yellow solid, mp: 147.3-149.2°C. 1 H NMR(400MHz,DMSO-d6)δ8.43(s,1H),7.86-7.79(m,2H),7.75(s,1H),7.68-7.57(m,2H),7.43(d,J=8.3Hz,1H),7.33 (td,J=7.6,1.1Hz,1H),7.16(dd,J=8.1,1.7Hz,1H),4.68(d,J=14.7Hz,1H),3.77(d,J=14.7Hz,1H),2.36(s,3H)ppm. 13 C NMR(101MHz,DMSO-d6)δ21.31,37.12,75.39(q,J=29.1Hz),116.35,118.55,121.92,122.63,123.12,125.32, 125.49(q,J=289.1Hz),126.98,129.80,132.45,133.48,136.10,145.64,152.89,153.84,158.63,164.48ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.27ppm.HRMS(ESI):m / zcalcdforC 20 H 14 F3NO3S[MH] - 404.05682,found404.05228.

[0126]

[0127] Compound 3ec.PE:EA=5:1,R f =0.52, white solid, mp: 154.6-156.9℃. 1H NMR (400MHz, DMSO-d6) δ8.41(s,1H),8.10(d,J=2.4Hz,1H),7.85-7.80(m,2H),7.76(dd,J=8.8,2.4Hz,1H),7.61(s,1H ),7.40(d,J=8.8Hz,1H),7.15(dd,J=8.3,1.7Hz,1H),4.66(d,J=14.7Hz,1H),3.76(d,J=14.7Hz,1H),2.35(s,3H)ppm. 13 C NMR (101MHz, DMSO-d6) δ21.31, 37.00, 75.41 (q, J = 29.8Hz), 116.93, 118.65, 120.39, 121.92, 122. 64,123.95,124.51,127.00,131.80,132.40,135.77,136.12,144.44,152.91,158.11,164.35ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.13ppm.HRMS(ESI):m / z calcd for C 20 H 13 BrF3NO3S[M+H] + 483.9830, found 483.9834.

[0128]

[0129] Compound 3ed.PE:EA=5:1,R f =0.4, pale yellow solid, mp: 195.3-196.9℃. 1 H NMR (400MHz, DMSO-d6) δ8.39(s,1H),7.83(d,J=8.1Hz,1H),7.75(s,1H),7.64(d,2H),7.29(ddd,J=24.4,16.0, 8.1Hz,3H),7.16(d,J=8.0Hz,1H),4.68(d,J=14.6Hz,1H),3.89(s,3H),3.76(d,J=14.7Hz,1H),2.36(s,3H)ppm. 13CNMR(101MHz, DMSO-d6) δ 21.31, 37.13, 56.57, 75.36 (q, J=29.1Hz), 115.46, 119.09, 120.74, 121.93, 122.65, 123.26, 125.29, 125.48 (q, J=289.0Hz), 126.98, 132.46, 136.10, 143.17, 145.90, 146.61, 152.88, 158.35, 164.47 ppm. 19 F NMR(377MHz, DMSO-d6) δ -77.30 ppm. HRMS(ESI): m / z calcd for C 21 H 16 F3NO4S [M-H] - 434.06739, found 434.06253.

[0130]

[0131] Compound 3ef. PE:EA = 5:1, R f = 0.35, white solid, mp: 198.1 - 199.9 °C. 1 H NMR(400MHz, DMSO-d6) δ 9.10 (s, 1H), 8.40 (d, J=8.4Hz, 1H), 8.22 (d, J=9.1Hz, 1H), 8.04 (dd, J=8.2, 1H), 7.83 (s, 1H), 7.78 (d, J=8.2Hz, 1H), 7.73 (t, J=7.7Hz, 1H), 7.65 - 7.56 (m, 3H), 4.76 (d, J=14.7Hz, 1H), 3.82 (d, J=14.7Hz, 1H), 2.32 (s, 3H) ppm. 13 C NMR(101MHz, DMSO-d6) δ 21.28, 37.12, 75.75 (q, J=29.1Hz), 112.46, 116.74, 121.90, 122.28, 122.63, 125.56 (q, J=288.4Hz), 126.86, 126.94, 129.00, 129.33, 129.54, 130.39, 132.47, 135.01, 136.06, 140.83, 152.87, 153.99, 158.71, 164.56 ppm. 19 F NMR(377MHz, DMSO-d6) δ -77.33 ppm. HRMS(ESI): m / z calcd for C 24 H 16F3NO3S[MH] - 454.07247, found 454.06749.

[0132]

[0133] Compound 3eg.PE:EA=5:1,R f =0.53, white solid, mp: 208.1-209.4℃. 1 H NMR (400MHz, DMSO-d6) δ8.42(s,1H),8.14-8.08(m,2H),7.87(s,1H),7.82(d,J=8.2Hz,1H),7.61(s ,1H),7.14(dd,J=8.3,1.6Hz,1H),4.63(d,J=14.8Hz,1H),3.78(d,J=14.8Hz,1H),2.34(s,3H)ppm. 13 C NMR(101MHz,DMSO-d6)δ21.31,36.96,75.42(q,J=29.3Hz),110.30,117.03,121.28,121.92,122.66,125.28, 125.32(q,J=289.1Hz),127.00,131.52,132.43,136.12,137.74,144.44,149.83,152.92,157.42,164.27ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.08ppm.HRMS(ESI):m / z calcd for C 20 H 12 Br2F3NO3S[M+H] + 561.8935, found 561.8939.

[0134]

[0135] Compound 3eh.PE:EA=5:1,R f =0.53, white solid, mp: 192.1-194.2℃. 1 H NMR(400MHz,DMSO-d6)δ8.44(s,1H),7.92(d,J=18.3Hz,2H),7.85-7.72(m,2H),7.60(s,1 H),7.12(d,J=8.3Hz,1H),4.65(d,J=14.8Hz,1H),3.79(d,J=14.8Hz,1H),2.32(s,3H)ppm. 13CNMR(101MHz,DMSO-d6)δ21.25,36.92,75.46(q,J=29.3Hz),120.84,121.02,121.84,122.64,125.44,125.30( q, J=289.2Hz),126.94,127.93,129.03,132.31,132.42,136.07,144.42,148.30,152.94,157.26,164.25ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.10ppm.HRMS(ESI):m / zcalcdfor C 20 H 12 Cl2F3NO3S[MH] - 471.97888, found 471.97346.

[0136]

[0137] Compound 3fa.PE:EA=5:1,R f =0.37, light yellow solid, mp: 156.4-158.1℃. 1 H NMR(400MHz, DMSO-d6)δ8.46(s,1H),7.99(dd,J=8.9,5.4Hz,1H),7.87-7.76(m,2H),7.67(dd,J=9.8,2.6Hz,1H),7.59(ddd,J=8.7,7.4, 1.6Hz,1H),7.39(d,J=8.3Hz,1H),7.29(t,J=7.5Hz,1H),7.21(td,J=9.0,2.6Hz,1H),4.74(d,J=14.7Hz,1H),3.82(d,J=14.8Hz,1H)ppm. 13 CNMR(101MHz,DMSO-d6)δ37.36,75.35(q,J=29.1Hz),108.60,108.83,113.81,114.05,116.30,118.53,122.92,123.68,123.78 ,125.23,125.46(q,J=289.0Hz),129.77,131.33,133.42,145.88,153.20,153.32,153.86,158.66,160.28,162.68,167.52ppm. 19FNMR(377MHz,DMSO-d6)δ-116.36,-77.37ppm.HRMS(ESI):m / z calcd for C 19 H 11 F4NO3S[M+H] + 410.0474, found 410.0478.

[0138]

[0139] Compound 3ga.PE:EA=5:1,R f =0.37, white solid, mp: 194.3-195.2℃. 1 H NMR(400MHz,DMSO-d6)δ8.42(s,1H),7.85-7.73(m,2H),7.67-7.55(m,3H),7.41(d,J=8.3Hz,1H),7 .31(t,J=7.5Hz,1H),4.66(d,J=14.6Hz,1H),3.74(d,J=14.7Hz,1H),2.22(s,3H),2.20(s,3H)ppm. 13 C NMR (101MHz, DMSO-d6) δ19.98, 19.99, 36.99, 75.38 (q, J = 29.2Hz), 116.32, 118.53, 121.93, 122.77, 123.14, 125. 28,125.51(q,J=289.2Hz),129.77,132.82,133.42,134.62,135.32,145.61,151.27,153.83,158.58,162.99ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.21ppm.HRMS(ESI):m / zcalcd for C 21 H 16 F3NO3S[M+H] + 420.0881, found 420.0885.

[0140]

[0141] Compound 3ha.PE:EA=5:1,R f =0.42, orange-yellow solid, mp: 165.4-166.8℃. 1HNMR(400MHz,DMSO-d6)δ8.42(s,1H),8.36-8.29(m,1H),8.02(d,J=8.7Hz,1H),7.98-7.89(m,1H),7.84-7.71(m,3H) ,7.61(t,J=7.3Hz,1H),7.55-7.44(m,3H),7.27(t,J=7.5Hz,1H),4.85(d,J=14.7Hz,1H),3.90(d,J=14.8Hz,1H)ppm. 13 CNMR(101MHz,DMSO-d6)δ36.84,75.74(q,J=29.1Hz),116.24,118.68,119.92,123.18,123.94,125.17,125.57(q,J=289.0H z),125.86,126.48,127.31,127.90,128.58,129.66,131.81,132.07,133.24,145.00,148.41,153.93,158.96,163.81ppm. 19 F NMR(377MHz,DMSO-d6)δ-77.09ppm.HRMS(ESI):m / z calcd for C 23 H 14 F3NO3S[M+H] + 442.0725,found442.0729.

[0142] Combination Fig. 27 The crystal data of compound 3ea are shown in Table 3.

[0143] Table 3 Crystal data of compound 3ea

[0144]

[0145] The activity of the above-synthesized compounds was tested by the following method:

[0146] Antibacterial test: According to the agricultural industry standard of the People's Republic of China (NY / T1156.2-2006), the mycelium growth rate method was used to determine the bactericidal or antibacterial activity of the compounds. The specific process is as follows:

[0147] The obtained pathogens were activated and cultured a few days before the experiment. The codes and names of the tested strains are: A: Rhizoctonia solani, B: Fusarium moniliforme, C: Fusarium graminearum, D: Fusarium oxysporum, and E: Phytophthora nicotianae.

[0148] Take 16.6 mg of the test sample and dissolve it in 0.66 mL of DMSO, then add an aqueous solution containing 0.1% Tween 80 to make a 500 μg / mL original drug. Pipette an appropriate amount of each test agent into a conical flask under sterile conditions, shake it thoroughly, and then pour an equal amount into three culture dishes with a diameter of 9 cm. The above experiment sets the treatment without the agent as a blank control, and each treatment is repeated three times. The commonly used pesticide triadimefon is used as the control group for the antibacterial activity determination. Cut the bacterial cake along the edge of the colony with a 5 mm diameter puncher under sterile conditions, inoculate the bacterial cake in the center of the drug-containing plate with an inoculator, with the mycelium side facing up, cover the dish, and place the culture dish in a constant temperature incubator at 25 degrees Celsius for cultivation. When the diameter of the control colony expands to more than 6 cm, measure the colony diameter using the cross method and take the average value; calculate the antibacterial rate at the end of the culture, and the calculation formula is:

[0149] Bacterial inhibition rate I = (D0-D t ) / D0*100%;

[0150] Among them, D0 is the average diameter of mycelium in the control disk, D t is the average diameter of mycelium in the sample disk; the comparison of the antibacterial effects of different compounds on six pathogens is shown in Table 4.

[0151] Table 4 Antibacterial effect data of each compound

[0152] Compound A B C D E 3ab 81±0 53±1 45±1 48±1 43±1 3ac 95±1 55±0 41±2 36±0 54±1 3ad 85±0 68±0 43±0 78±0 85±0 3ae 85±1 67±1 45±0 47±1 67±0 3af 79±2 73±0 62±1 39±0 40±1 3ba 97±0 65±2 33±0 46±0 68±1 3bb 75±1 63±0 48±1 50±1 69±0 3bc 79±0 50±1 62±1 46±0 55±2 3be 83±1 72±1 38±0 28±0 68±0 3bf 76±1 47±1 41±2 58±0 48±1 3ca 96±0 55±0 63±1 34±0 42±0 3cd 80±1 64±1 <10 82±0 60±1 3ce 67±2 37±2 25±1 <10 26±1 3cf 66±1 66±0 83±0 22±0 36±0 3da 78±0 53±1 61±1 19±0 68±0 3dc 76±1 47±2 18±0 43±0 69±1 3dd 64±1 48±1 44±1 74±1 43±1 3ea 98±0 89±0 65±1 80±0 71±0 3ec 87±1 90±1 56±1 45±1 39±1 3ed 99±0 53±0 43±2 69±0 67±2 3ef 76±1 51±1 52±0 41±0 63±1 3eg 75±1 57±0 78±0 52±1 62±0 3eh 67±1 48±1 41±1 34±0 25±2 3fa 93±1 87±0 44±0 57±0 73±1 3ga 57±0 56±0 23±0 <10 38±0 3ha 79±1 64±1 54±1 39±0 74±1 Triadimefon 70±0 85±1 45±0 41±0 30±1

[0153] As can be seen from the data in Table 4, compared with the control group, the above-mentioned compound prepared by the present invention has a better antibacterial effect on one or more of Rhizoctonia solani, Fusarium moniliforme, Fusarium graminearum, Fusarium oxysporum and tobacco black leg pathogen. The compound in the present invention can exist in pure form, or it can be combined with one or more of commercial bactericides to prepare a composite antibacterial agent. The antibacterial agent can be processed into emulsifiable concentrate, aqueous solution, powder, wettable powder, water dispersible granule or other suitable dosage form according to specific use requirements.

[0154] As can be seen from the above, the present invention introduces the active substructure of benzothiazole into the skeleton structure of trifluoromethyl tertiary alcohol, designs and synthesizes a series of novel benzothiazole compounds, which have a good inhibitory effect on agricultural pathogens, and are conducive to the further development of highly antibacterial antibacterial agents to meet the use needs. In addition, in the preparation process of the present invention, no catalyst is used, the reaction conditions are mild, the process is simple, and it is easy to implement, which is very suitable for large-scale production and application, and provides a simple method support for further research on such derivatives.

[0155] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, they are also intended to be included.

Claims

1. A tertiary alcohol derivative containing trifluoromethylbenzothiazole, characterized in that: The structural formula of the trifluoromethylbenzothiazole tertiary alcohol derivative is: Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; Or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

2. The trifluoromethylbenzothiazole tertiary alcohol derivative according to claim 1, characterized in that: Alkyl is methyl, alkoxy is methoxy, and halogen is fluorine, chlorine or bromine.

3. The trifluoromethylbenzothiazole tertiary alcohol derivative according to claim 1, characterized in that: Specifically, the following compounds:

4. The method for preparing a trifluoromethylbenzothiazole tertiary alcohol derivative according to claim 1, characterized in that: The following steps are involved: Using the compound of formula 1 and the compound of formula 2 as raw materials and cyclopentane as solvent, a trifluoromethylbenzothiazole tertiary alcohol derivative shown in formula 3 is prepared by carbon-hydrogen bond functionalization; Its synthetic route is as follows: Among them, R 1 , R 2 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halogen; or, R 1 , R 2 Each independently forms a naphthalene ring with the substituted benzene ring.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the compound of formula 1 to the compound of formula 2 is 1:

1.

6. The preparation method according to claim 4, characterized in that: The reaction was stirred at 120°C to 130°C for 4h to 13h.

7. The preparation method according to claim 6, characterized in that: The temperature is 120°C and the reaction time is 8h to 12h.

8. The preparation method according to claim 4, characterized in that: After the reaction is completed, the product can be purified by column chromatography.

9. Use of the trifluoromethylbenzothiazole tertiary alcohol derivative or its pesticide acceptable salt according to claim 1 in the preparation of agricultural antibacterial agents.

10. The use according to claim 9, characterized in that: The agricultural antibacterial agent is used for inhibiting one or more of Rhizoctonia solani, Fusarium moniliforme, Fusarium graminearum, Fusarium oxysporum and Nicotiana tabacum black shank pathogen.

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