Hydrazide compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pesticide chemistry, and particularly relates to a hydrazide compound as well as a preparation method and application thereof. The hydrazide compound has a structure as shown in a formula I; the skeleton of the novel hydrazide compound is different from that of a traditional commercially available antibacterial agent, the structure is novel, the novel hydrazide compound can be applied to agriculture and solve the problem of drug resistance of plant pathogenic bacteria, and a new choice is provided for research, development and application of agricultural chemicals. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticide chemistry, and in particular relates to a hydrazide compound and a preparation method and application thereof. Background Art

[0002] Plant pathogens are one of the major factors that lead to reduced grain production and threaten food quality. The long-term use of agricultural fungicides has led to a sharp increase in drug resistance in plant pathogens, as well as large-scale environmental pollution, making disease control increasingly difficult. Summary of the Invention

[0003] The present invention aims to provide a hydrazide compound, a preparation method and application thereof. The hydrazide compound provided by the present invention has a novel structure, expands the structural framework of agricultural fungicides, and has good antibacterial properties against Ralstonia solanacearum, Xanthomonas campestris, Bacillus michiganensis and Pseudomonas syringae.

[0004] In order to achieve the above object, the present invention provides the following technical solutions:

[0005] The present invention provides a hydrazide compound having a structure shown in Formula I:

[0006] In formula I, R is naphthyl or substituted phenyl.

[0007] Preferably, the substituent of the substituted phenyl group is methyl or halogen.

[0008] Preferably, the substituted phenyl group is a structure represented by formula (1) to (24):

[0009]

[0010]

[0011] The present invention also provides a method for preparing the hydrazide compound described in the above technical solution, comprising the following steps:

[0012] Compound 1 and oxalyl chloride are first dissolved, and the obtained first solution is subjected to a first substitution reaction to obtain compound 2;

[0013]

[0014] Dissolving the compound 2 and methanol for a second time, and subjecting the obtained second solution to a second substitution reaction to obtain compound 3;

[0015]

[0016] The compound 3 and sulfuryl chloride are dissolved for a third time, and the obtained third solution is subjected to a third substitution reaction to obtain compound 4;

[0017]

[0018] Dissolving the compound 4 and hydrazine hydrate for the fourth time, and subjecting the obtained fourth solution to a fourth substitution reaction to obtain compound 5;

[0019]

[0020] Dissolving the compound 5 and the compound I-1 having the structure shown in Formula I-1 for the fifth time, and subjecting the obtained fifth solution to a fifth substitution reaction to obtain the hydrazide compound;

[0021]

[0022] Preferably, the molar ratio of the compound 1 to oxalyl chloride is 1:2-4; the temperature of the first substitution reaction is room temperature, and the time is 2-4 hours.

[0023] Preferably, the usage ratio of the compound 2 and methanol is 1 mmol:8-12 mL; the temperature of the second substitution reaction is room temperature, and the time is 2.5-4 h.

[0024] Preferably, the usage ratio of the compound 3 and sulfuryl chloride is 1 mmol:4-6 mL, and the temperature of the third substitution reaction is room temperature, and the time is 2-5 h.

[0025] Preferably, the molar ratio of the compound 4 to hydrazine hydrate is 1:4-6; the fourth substitution reaction is carried out under reflux conditions for 3-5 hours.

[0026] Preferably, the molar ratio of compound 5 to compound I-1 is 1:1 to 1.5; the temperature of the fifth substitution reaction is room temperature, and the time is 2.5 to 4 hours.

[0027] The present invention also provides the use of the hydrazide compound described in the above technical solution or the hydrazide compound prepared by the preparation method described in the above technical solution in antibacterial treatment, wherein the bacteria include one or more of Ralstonia solanacearum, Xanthomonas campestris, Bacillus michiganensis and Pseudomonas syringae.

[0028] The present invention provides a hydrazide compound having a structure shown in Formula I:

[0029] In formula I, R is naphthyl or substituted phenyl.

[0030] The novel hydrazide compound provided by the present invention has a skeleton different from traditional commercially available antibacterial agents and a novel structure. It can be applied to agriculture and solve the problem of drug resistance of plant pathogenic bacteria, providing a new option for the research and development and application of agricultural chemicals. DETAILED DESCRIPTION

[0031] The present invention provides a hydrazide compound having a structure shown in Formula I:

[0032]

[0033] In formula I, R is naphthyl or substituted phenyl.

[0034] As an embodiment of the present invention, the substituent of the substituted phenyl group may be a methyl group or a halogen group; the halogen group may be a Cl - 、F - and Br - One or more of the .

[0035] As an embodiment of the present invention, the substituted phenyl group may specifically be a structure shown in formula (1) to (24):

[0036]

[0037] The present invention also provides a method for preparing the hydrazide compound described in the above technical solution, comprising the following steps:

[0038] Compound 1 and oxalyl chloride are first dissolved, and the obtained first solution is subjected to a first substitution reaction to obtain compound 2;

[0039]

[0040] Dissolving the compound 2 and methanol for a second time, and subjecting the obtained second solution to a second substitution reaction to obtain compound 3;

[0041]

[0042] The compound 3 and sulfuryl chloride are dissolved for a third time, and the obtained third solution is subjected to a third substitution reaction to obtain compound 4;

[0043]

[0044] Dissolving the compound 4 and hydrazine hydrate for the fourth time, and subjecting the obtained fourth solution to a fourth substitution reaction to obtain compound 5;

[0045]

[0046] Dissolving the compound 5 and the compound I-1 having the structure shown in Formula I-1 for the fifth time, and subjecting the obtained fifth solution to a fifth substitution reaction to obtain the hydrazide compound;

[0047]

[0048] The present invention first dissolves compound 1 and oxalyl chloride, and then performs a first substitution reaction on the obtained first solution to obtain compound 2.

[0049] As an embodiment of the present invention, the molar ratio of the compound 1 and oxalyl chloride can be 1:2 to 4, specifically 1:3; the first dissolving solvent can be dichloromethane; as an embodiment of the present invention, the first substitution reaction is preferably carried out under DMF conditions, and the molar ratio of the DMF and compound 1 can be 0.05 to 0.2:1, specifically 0.1:1.

[0050] As an embodiment of the present invention, the temperature of the first substitution reaction can be room temperature, and the time of the first substitution reaction can be 2 to 4 hours, specifically 3 hours. As an embodiment of the present invention, after the first substitution reaction, the system obtained by the first substitution reaction is further concentrated under reduced pressure to obtain compound 2.

[0051] After obtaining compound 2, the present invention dissolves compound 2 and methanol for a second time, and the obtained second solution undergoes a second substitution reaction to obtain compound 3.

[0052] As an embodiment of the present invention, the ratio of the compound 2 to methanol can be 1 mmol: 8-12 mL, specifically 1 mmol: 10 mL. As an embodiment of the present invention, the second dissolution solvent can be dichloromethane; the second dissolution is preferably to dissolve the compound 2 in dichloromethane and then add methanol under ice bath.

[0053] As an embodiment of the present invention, the temperature of the second substitution reaction can be room temperature, specifically 25° C., and the time can be 2.5 to 4 hours, specifically 3 hours.

[0054] As an embodiment of the present invention, after the second substitution reaction, the system obtained by the second substitution reaction is purified by column chromatography; the eluents for purification by column chromatography are petroleum ether and ethyl acetate; the volume ratio of petroleum ether and ethyl acetate can be 40:1.

[0055] After obtaining compound 3, the present invention performs a third dissolution of compound 3 and sulfuryl chloride, and the obtained third dissolution solution undergoes a third substitution reaction to obtain compound 4.

[0056] As an embodiment of the present invention, the usage ratio of the compound 3 and sulfuryl chloride can be 1 mmol:4-6 mL, specifically 1 mmol:5 mL. As an embodiment of the present invention, the fourth dissolving solvent can be dichloromethane.

[0057] As one embodiment of the present invention, the temperature of the third substitution reaction can be room temperature, specifically 25°C, and the time can be 2 to 5 hours, specifically 4 hours. As one embodiment of the present invention, after the third substitution reaction, the system obtained by the third substitution reaction is further recrystallized. As one embodiment of the present invention, the recrystallization method can be to dissolve the crude product in a purification solvent, and after drying the resulting solution, obtain compound 4; the purification solvent can be a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent of petroleum ether and ethyl acetate can be 5:1.

[0058] After obtaining compound 4, the present invention performs a fourth dissolution of compound 4 and hydrazine hydrate, and the obtained fourth dissolution solution undergoes a fourth substitution reaction to obtain compound 5.

[0059] As an embodiment of the present invention, the molar ratio of the compound 4 to hydrazine hydrate may be 1:4 to 6, specifically 1:5. As an embodiment of the present invention, the fourth dissolving solvent may be ethanol.

[0060] As an embodiment of the present invention, the fourth substitution reaction is preferably carried out under reflux conditions; the fourth substitution reaction time can be 3 to 5 hours, specifically 4 hours. As an embodiment of the present invention, after the third substitution reaction, the system obtained by the fourth substitution reaction is further recrystallized. As an embodiment of the present invention, the recrystallization method can be to dissolve the crude product in ethanol, and after drying the solvent of the resulting solution, obtain Compound 5.

[0061] After obtaining compound 5, the present invention performs a fifth dissolution of compound 5 and compound I-1 having a structure represented by formula I-1, and the obtained fifth dissolution solution is subjected to a fifth substitution reaction to obtain the hydrazide compound.

[0062] As an embodiment of the present invention, the molar ratio of the compound 5 to the compound I-1 may be 1:1 to 1.5, specifically 1:1.2. As an embodiment of the present invention, the fifth dissolving solvent may be dichloromethane.

[0063] As an embodiment of the present invention, the fifth substitution reaction is preferably carried out under catalyst conditions, and the catalyst is pyridine and DMAP; the molar ratio of the compound 5 to the pyridine can be 1:1 to 1.5, specifically 1:1.2; the molar ratio of the pyridine to DMAP can be 10 to 15:1, specifically 12:1.

[0064] As an embodiment of the present invention, the temperature of the fifth substitution reaction can be room temperature, and the time can be 2.5 to 4 hours.

[0065] As an embodiment of the present invention, after the fifth substitution reaction, the method further comprises purifying the system obtained by the fifth substitution reaction by column chromatography; the eluents for purification by column chromatography are petroleum ether and ethyl acetate; during elution, the volume ratio of petroleum ether to ethyl acetate is 5:1→3:1.

[0066] In the present invention, the synthetic route of the hydrazide compound is as follows:

[0067]

[0068] The present invention also provides the use of the hydrazide compounds described in the above technical solution in antibacterial applications, wherein the bacteria include one or more of Ralstonia solanacearum, Xanthomonas campestris, Cladosporium michiganensis and Pseudomonas syringae.

[0069] In order to further illustrate the present invention, the scheme of the present invention is described in detail below with reference to the embodiments, but they should not be understood as limiting the scope of protection of the present invention.

[0070] Example 1

[0071] Compound TSSJ1:

[0072]

[0073] (1) Preparation of compounds 2 to 5:

[0074] In a 100 mL round-bottom flask, 1 mmol of compound 1 and 3 mmol of oxalyl chloride were dissolved in 20 mL of dichloromethane under ice bath. 0.1 mmol of DMF was added dropwise. The mixture was reacted at room temperature for 3 h. After the reaction, compound 2 was obtained by rotary evaporation under reduced pressure with a yield of 78%.

[0075] In a 100 mL round-bottom flask, 1 mmol of compound 2 was dissolved in 20 mL of dichloromethane. 10 mL of methanol was added under ice-bath conditions. The mixture was reacted at 25°C for 3 h and then purified by column chromatography using a ratio of petroleum ether to ethyl acetate (40:1) as the eluent to obtain brown crystalline compound 3 in a yield of 95%.

[0076] In a 100-mL round-bottom flask, 1 mmol of compound 3 was dissolved in 20 mL of dichloromethane, and 5 mL of sulfuryl chloride was added. The mixture was reacted at 25°C for 4 h to obtain a crude product. The crude product was dissolved in petroleum ether and ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1). The solvent was dried to obtain compound 4 with a yield of 82%.

[0077] In a 100 mL round-bottom flask, 1 mmol of compound 4 was dissolved in 20 mL of ethanol, and 5 mmol of hydrazine hydrate was added. After reflux for 4 h, the crude product was dissolved in 50 mL of ethanol. After drying the solvent, compound 5 was obtained with a yield of 72%.

[0078] (2) Preparation of compound TSSJ1 from compound 5

[0079] In a 100 mL round-bottom flask, 1 mmol of compound 5 and 1.2 mmol of compound I-1 (where R is formula (1)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. The mixture was reacted at room temperature for 3 h and then purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ1 with a yield of 63%.

[0080] The NMR data of compound TSSJ1 are: 1 H NMR (400MHz, Acetone-d6) δ11.64(s,1H),9.80(s,1H),8.64(s,1H),7.81-7.70(m,2H),7.32(d,J=10.4Hz,2H),6.98(s,1H),2.40(s,3H); HR-MS(m / z)calcd for C 12 H 11 Cl2N3O3S[M+Na] + :369.9790;found:369.9797.

[0081] Example 2

[0082] Compound TSSJ2

[0083]

[0084] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0085] (2) Compound TSSJ2 was prepared from compound 5;

[0086] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (2)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ2 with a yield of 64%.

[0087] The NMR data of compound TSSJ2 are 1H NMR (400MHz, Acetone-d6) δ11.74 (s, 1H), 10.01 (s, 1H), 9.40 (d, J = 39.0Hz, 1H), 7.24-7.04 (m, 2H), 6.99 (s, 1H); HR-MS (m / z)calcd forC 11 H6Cl2F3N3O3S[M+Na] + :409.9351;found:409.9358.

[0088] Example 3

[0089] Compound TSSJ3

[0090]

[0091] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0092] (2) Compound TSSJ3 was prepared from compound 5;

[0093] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (3)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ3 with a yield of 59%.

[0094] The NMR data of compound TSSJ3 are 1 H NMR(400MHz, Acetone-d6)δ11.71(s,1H),9.93(s,1H),9.21(s,1H),7.73(t,J=6.7Hz,2H),6.99(s,1H); HR-MS(m / z)calcd forC 11 H6Cl2F3N3O3S[M+Na] + :409.9351;found:409.9360.

[0095] Example 4

[0096] Compound TSSJ4

[0097]

[0098] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0099] (2) Compound TSSJ4 was prepared from compound 5;

[0100] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (4)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate 5:1→3:1 to obtain compound TSSJ4 with a yield of 66%.

[0101] The NMR data of compound TSSJ4 are 1 H NMR (400MHz, Acetone-d6) δ11.72(s,1H),9.92(s,1H),9.19(s,1H),7.61-7.47(m,2H),7.39(tt,J=9.0,2.4Hz,1H),6.99(s,1H); HR-MS(m / z)calcd for C 11 H6Cl2F2N3O3S[M+Na] + :391.9445;found:391.9451.

[0102] Example 5

[0103] Compound TSSJ5

[0104]

[0105] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0106] (2) Compound TSSJ5 was prepared from compound 5;

[0107] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (5)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate 5:1→3:1 to obtain compound TSSJ5 with a yield of 63%.

[0108] The NMR data of compound TSSJ5 are 1 H NMR (400MHz, Acetone-d6) δ11.53(s,1H),9.76(s,1H),8.96(s,1H),8.89-8.81(m,1H),8.27-8.19(m,2H),8.06(dd ,J=7.3,2.0Hz,1H),7.67(pd,J=6.9,1.6Hz,2H),7.59(t,J=7.8Hz,1H),6.89(d,J=1.9Hz,1H); HR-MS(m / z)calcdfor C 15 H 11Cl2N3O3S[M+Na] + :405.9790;found:405.9797.

[0109] Example 6

[0110] Compound TSSJ6

[0111]

[0112] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0113] (2) Compound TSSJ6 was prepared from compound 5;

[0114] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (6)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ6 with a yield of 61%.

[0115] The NMR data of compound TSSJ6 are 1 H NMR (400MHz, Acetone-d6) δ11.72(s,1H),9.92(s,1H),9.13(s,1H),8.03(d,J =2.1Hz, 1H), 7.83 (dd, J = 8.4, 2.1Hz, 1H), 7.77 (d, J = 8.4Hz, 1H), 6.99 (s, 1H).

[0116] Example 7

[0117] Compound TSSJ7

[0118]

[0119] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0120] (2) Compound TSSJ7 was prepared from compound 5;

[0121] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (7)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ7 with a yield of 58%.

[0122] The NMR data of compound TSSJ7 are: 1H NMR (400MHz, Acetone-d6) δ11.51(s,1H),9.76(s,1H),9.08(s,1H),7.83(d,J=2.3Hz,1H),7.55(d,J=2.3Hz,1H),7.54(s,1H),6.82(s,1H).

[0123] Example 8

[0124] Compound TSSJ8

[0125]

[0126] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0127] (2) Compound TSSJ8 was prepared from compound 5;

[0128] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (8)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ8 with a yield of 66%.

[0129] The NMR data of compound TSSJ8 are 1 H NMR (400MHz, Acetone-d6) δ11.83(s,1H),9.78(s,1H),9.57(s,1H),7.83(s,1 H), 7.70 (d, J = 7.3Hz, 1H), 7.62-7.57 (m, 1H), 7.43-7.38 (m, 1H), 7.05 (s, 1H).

[0130] Example 9

[0131] Compound TSSJ9

[0132]

[0133] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0134] (2) Compound TSSJ9 was prepared from compound 5;

[0135] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (9)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ9 with a yield of 68%.

[0136] The NMR data of compound TSSJ9 are: 1 H NMR (400MHz, Acetone-d6) δ11.51(s,1H),9.70(s,1H),8.93(s,1H),7.86(d,J=8.5 Hz, 1H), 7.59 (d, J = 2.1Hz, 1H), 7.38 (dd, J = 8.5, 2.1Hz, 1H), 6.81 (d, J = 2.2Hz, 1H).

[0137] Example 10

[0138] Compound TSSJ10

[0139]

[0140] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0141] (2) Compound TSSJ10 was prepared from compound 5;

[0142] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (10)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ10 with a yield of 67%.

[0143] The NMR data of compound TSSJ10 are: 1 H NMR (400MHz, Acetone-d6) δ11.55(s,1H),9.75(s,1H),9.03(s,1H),7.62(dd,J=8.4,7.5Hz,1H), 7.50(dd,J=9.6,1.8Hz,1H),7.39(dd,J=8.5,1.8Hz,1H),6.84(d,J=2.0Hz,1H); HR-MS(m / z)calcd for C 11 H7BrCl2FN3O3S[M+Na] + :451.8645;found:451.8653.

[0144] Example 11

[0145] Compound TSSJ11

[0146]

[0147] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0148] (2) Compound TSSJ11 was prepared from compound 5;

[0149] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (11)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ11 with a yield of 64%.

[0150] The NMR data of compound TSSJ11 are: 1 H NMR (400MHz, Acetone-d6) δ11.52(s,1H),9.68(s,1H),8.67(s,1H),7.79-7.73(m,2H),7.51( s,1H),7.48(d,J=2.3Hz,1H),6.85(d,J=2.5Hz,1H),4.62(d,J=36.3Hz,2H); HR-MS(m / z)calcd for C 12 H 10 Cl2BrN3O3S[M+Na] + :447.8896;found:447.8906.

[0151] Example 12

[0152] Compound TSSJ12

[0153]

[0154] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0155] (2) Compound TSSJ12 was prepared from compound 5;

[0156] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (12)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ12 with a yield of 60%.

[0157] The NMR data of compound TSSJ12 are: 1H NMR (400MHz, Acetone-d6) δ11.63(s,1H),9.82(s,1H),8.86(s,1H),8.06(dd,J=7.4,2.1Hz, 1H),7.85(dd,J=7.4,1.7Hz,1H),7.58-7.50(m,2H),6.95(d,J=2.7Hz,1H); HR-MS(m / z)calcd for C 11 H8Cl2BrN3O3S[M+Na] + :433.8739;found:433.8753.

[0158] Example 13

[0159] Compound TSSJ13

[0160]

[0161] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0162] (2) Compound TSSJ13 was prepared from compound 5;

[0163] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (13)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ13 with a yield of 61%.

[0164] The NMR data of compound TSSJ13 are: 1 H NMR (400MHz, Acetone-d6) δ11.66(s,1H),9.88(s,1H),9.01(s,1H),7.86(ddd,J=9.8,7.4,2.2Hz,1H),7.7 7(ddt,J=8.2,4.0,1.8Hz,1H),7.53(ddd,J=10.3,8.7,7.7Hz,1H),7.00(d,J=1.9Hz,1H); HR-MS(m / z)calcd forC 11 H7Cl2F2N3O3S[M+Na] + :391.9445;found:391.9453.

[0165] Example 14

[0166] Compound TSSJ14

[0167]

[0168] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0169] (2) Compound TSSJ14 was prepared from compound 5;

[0170] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (14)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ14 with a yield of 66%.

[0171] The NMR data of compound TSSJ14 are: 1 H NMR (400MHz, Acetone-d6) δ11.52(s,1H),9.71(s,1H),8.76(s,1H),7.79-7.73(m,2H),7.48-7.42(m,2H),6.86(d,J=2.6Hz,1H); HR-MS(m / z)calcd for C 11 H8Cl3N3O3S[M+Na] + :389.9244;found:389.9252.

[0172] Example 15

[0173] Compound TSSJ15

[0174]

[0175] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0176] (2) Compound TSSJ15 was prepared from compound 5;

[0177] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (15)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ15 with a yield of 65%.

[0178] The NMR data of compound TSSJ15 are: 1H NMR(400MHz, Acetone-d6)δ11.64(s,1H),9.83(s,1H),8.80(s,1H),7.98-7.95(m,2H),7.35-7.30(m,2H),7.00(s,1H); HR-MS(m / z)calcd forC 11 H8Cl2FN3O3S[M+Na] + :373.9540;found:373.9547.

[0179] Example 16

[0180] Compound TSSJ16

[0181]

[0182] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0183] (2) Compound TSSJ16 was prepared from compound 5;

[0184] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (16)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ16 with a yield of 69%.

[0185] The NMR data of compound TSSJ16 are: 1 H NMR(400MHz, Acetone-d6)δ11.66(s,1H),9.85(s,1H),8.91(s,1H),7.91-7.68(m,4H),7.01(s,1H); HR-MS(m / z)calcd for C 11 H8Cl2BrN3O3S[M+Na] + :433.8739;found:433.8753.

[0186] Example 17

[0187] Compound TSSJ17

[0188]

[0189] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0190] (2) Compound TSSJ17 was prepared from compound 5;

[0191] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (17)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate 5:1→3:1 to obtain compound TSSJ17 with a yield of 58%.

[0192] The NMR data of compound TSSJ17 are: 1 H NMR (400MHz, Acetone-d6) δ11.69(s,1H),9.97(s,1H),9.30(s,1H),7.69(s,2H),6.99(d,J=1.6Hz,1H); HR-MS(m / z)calcd for C 11 H6Cl5N3O3S[M+Na] + :457.8465;found:457.8473.

[0193] Example 18

[0194] Compound TSSJ18

[0195]

[0196] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0197] (2) Compound TSSJ18 was prepared from compound 5;

[0198] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (18)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ18 with a yield of 62%.

[0199] The NMR data of compound TSSJ18 are: 1 H NMR (400MHz, Acetone-d6) δ11.68(s,1H),9.89(s,1H),9.18(s,1H),7.93-7.80(m,1H),7.5 0(dd,J=9.8,2.0Hz,1H),7.38(ddd,J=8.5,2.0,0.8Hz,1H),6.98(s,1H); HR-MS(m / z)calcd for C 11 H7Cl2 37 ClFN3O3S[M+Na] +:409.9120;found:409.9126.

[0200] Example 19

[0201] Compound TSSJ19

[0202]

[0203] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0204] (2) Compound TSSJ19 was prepared from compound 5;

[0205] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (19)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate 5:1→3:1 to obtain compound TSSJ19 with a yield of 60%.

[0206] The NMR data of compound TSSJ19 are: 1 H NMR(400MHz, Acetone-d6)δ11.69(s,1H),9.90(s,1H),9.29(s,1H),8.10(s,1H),7.94(s,1H),6.97(s,1H); HR-MS(m / z)calcd forC 11 H6Cl5N3O3S[M+Na] + :457.8465;found:457.8475.

[0207] Example 20

[0208] Compound TSSJ20

[0209]

[0210] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0211] (2) Compound TSSJ20 was prepared from compound 5;

[0212] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (20)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ20 with a yield of 63%.

[0213] The NMR data of compound TSSJ20 are:1 H NMR (400MHz, Acetone-d6) δ11.54(s,1H),9.81(s,1H),9.12(s,1H),7.59(tt,J=8.5,6.0Hz,1H),7.09-6.97(m,2H),6.86(s,1H); HR-MS(m / z)calcd for C 11 H7Cl2F2N3O3S[M+Na] + :391.9945;found:391.9453.

[0214] Example 21

[0215] Compound TSSJ21

[0216]

[0217] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0218] (2) Compound TSSJ21 was prepared from compound 5;

[0219] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (21)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ21 with a yield of 66%.

[0220] The NMR data of compound TSSJ21 are: 1 H NMR (400MHz, Acetone-d6) δ11.47(s,1H),9.67(s,1H),8.95-8.58(m,1H),7.92-7.85(m, 1H),7.55-7.46(m,2H),7.33(ddd,J=8.5,6.0,2.7Hz,1H),6.81(s,1H); HR-MS(m / z)calcd for C 11 H8Cl2 37 ClN3O3S[M+Na] + :391.9215;found:391.9215.

[0221] Example 22

[0222] Compound TSSJ22

[0223] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0224] (2) Compound TSSJ22 was prepared from compound 5;

[0225] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (22)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate 5:1→3:1 to obtain compound TSSJ22 with a yield of 67%.

[0226] The NMR data of compound TSSJ22 are: 1 H NMR (400MHz, Acetone-d6) δ11.66(s,1H),9.87(s,1H),9.09(s,1H),7.90(td,J=8.5,6.3Hz,1H) ,7.27(ddd,J=10.2,9.1,2.5Hz,1H),7.19-7.07(m,1H),6.98(d,J=1.8Hz,1H); HR-MS(m / z)calcd for C 11 H7Cl2F2N3O3S[M+Na] + :391.9445;found:391.9455.

[0227] Example 23

[0228] Compound TSSJ23

[0229]

[0230] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0231] (2) Compound TSSJ23 was prepared from compound 5;

[0232] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (23)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ23 with a yield of 60%.

[0233] The NMR data of compound TSSJ23 are: 1H NMR (400MHz, Acetone-d6) δ11.65(s,1H),9.84(s,1H),9.08(s,1H),7.93(d,J=8.5Hz, 1H),7.88(d,J=1.9Hz,1H),7.68(dd,J=8.5,1.9Hz,1H),6.96(s,1H); HR-MS(m / z)calcd for C 11 H7Cl3BrN3O3S[M+Na] + :467.8349;found:467.8361.

[0234] Example 24

[0235] Compound TSSJ24

[0236]

[0237] (1) Compounds 2 to 5 were prepared in the same manner as in Example 1;

[0238] (2) Compound TSSJ24 was prepared from compound 5;

[0239] In a 100 mL round-bottom flask, 1 mmol of compound 5 and compound I-1 (R of formula (24)) were dissolved in 10 mL of dichloromethane. 1.2 mmol of pyridine and 0.1 mmol of DMAP were added. After reacting for 3 h, the mixture was purified by column chromatography with an eluent of petroleum ether:ethyl acetate (5:1→3:1) to obtain compound TSSJ24 with a yield of 62%.

[0240] The NMR data of compound TSSJ24 are: 1 H NMR (400MHz, Acetone-d6) δ11.49(s,1H),9.70(s,1H),8.85(s,1H),7.70(ddd,J=8.0, 7.0,1.7Hz,1H),7.63-7.54(m,1H),7.24-7.13(m,2H),6.83(s,1H); HR-MS(m / z)calcd for C 11 H8Cl2FN3O3S[M+Na] + :373.9540;found:373.9548.

[0241] Note: The NMR data of compounds TSSJ1 to TSSJ24 were detected by 1D / 2D NMR (one-dimensional nuclear magnetic resonance spectroscopy and two-dimensional nuclear magnetic resonance spectroscopy) and HRMS.

[0242] The antibacterial activity experiments were conducted on the compounds TSSJ1 to TSSJ24 prepared in Examples 1 to 24. The test method was as follows: the antibacterial activity of the target compound was determined by turbidity method. Five different concentration gradients were designed: 128 mg / L, 64 mg / L, 32 mg / L, 16 mg / L and 8 mg / L. 5 μL of bacterial solution was added to each of the gradients. The cells were cultured in a constant temperature incubator at 38°C for 18 h. The OD600 was measured by microplate reader and the EC50 was calculated. The antibacterial activity results are shown in Tables 1 to 2.

[0243] Table 1 Ralstonia solanacearum activity of TSSJ1 to TSSJ24

[0244]

[0245]

[0246] Table 2 Anti-three plant pathogenic fungi activity of TSSJ1-TSSJ24

[0247]

[0248]

[0249] From the above results, it can be seen that compounds TSSJ1-TSSJ24 all have good antibacterial activity and do not show obvious toxicity to non-target organisms; among them, TSSJ5 has better activity against Ralstonia solanacearum and Xanthomonas campestris, exceeding the positive control copper thiamethoxam.

[0250] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A hydrazide compound having the structure shown in Formula I: In formula I, R is naphthyl or substituted phenyl.

2. The hydrazide compound according to claim 1, wherein The substituent of the substituted phenyl group is a methyl group or a halogen group.

3. The hydrazide compound according to claim 2, wherein The substituted phenyl group is a structure represented by formula (1) to (24):

4. The method for preparing the hydrazide compound according to any one of claims 1 to 3, comprising the following steps: Compound 1 and oxalyl chloride are first dissolved, and the obtained first solution is subjected to a first substitution reaction to obtain compound 2; Dissolving the compound 2 and methanol for a second time, and subjecting the obtained second solution to a second substitution reaction to obtain compound 3; The compound 3 and sulfuryl chloride are dissolved for a third time, and the obtained third solution is subjected to a third substitution reaction to obtain compound 4; Dissolving the compound 4 and hydrazine hydrate for the fourth time, and subjecting the obtained fourth solution to a fourth substitution reaction to obtain compound 5; Dissolving the compound 5 and the compound I-1 having the structure shown in Formula I-1 for the fifth time, and subjecting the obtained fifth solution to a fifth substitution reaction to obtain the hydrazide compound; 5. The preparation method according to claim 4, wherein The molar ratio of the compound 1 to oxalyl chloride is 1:2-4; the temperature of the first substitution reaction is room temperature, and the time is 2-4 hours.

6. The preparation method according to claim 4, wherein The dosage ratio of the compound 2 and methanol is 1 mmol:8-12 mL; the temperature of the second substitution reaction is room temperature, and the time is 2.5-4 h.

7. The preparation method according to claim 4, wherein The usage ratio of the compound 3 and sulfuryl chloride is 1 mmol:4-6 mL. The temperature of the third substitution reaction is room temperature and the time is 2-5 h.

8. The preparation method according to claim 4, wherein The molar ratio of the compound 4 to hydrazine hydrate is 1:4-6; the fourth substitution reaction is carried out under reflux conditions for 3-5 hours.

9. The preparation method according to claim 4, wherein The molar ratio of the compound 5 to the compound I-1 is 1:1 to 1.5; the temperature of the fifth substitution reaction is room temperature, and the time is 2.5 to 4 hours.

10. Use of the hydrazide compound according to any one of claims 1 to 3 or the hydrazide compound prepared by the preparation method according to any one of claims 4 to 9 in antibacterial applications, characterized in that: The bacteria include one or more of Ralstonia solanacearum, Xanthomonas campestris, Cladosporium michiganensis and Pseudomonas syringae.

Images