426
T. MORI et al.
Table 2. Miticidal Activity of 2-Alkoxycarbonyltrifluoromethanesul-
fonanilides against Chelacaropsis moorei (Cm)
J ¼ 8:6 Hz), 7.96 (1H, d, J ¼ 2:2 Hz), 11.2 (1H, broad s).
n-Propyl 5-chloro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (3b): 62%; nD (25.5), 1.4898; NMR (250 MHz)
ꢀH (CDCl3): 1.05 (3H, m), 1.84 (2H, m), 4.35 (2H, m),
7.55 (1H, d, J ¼ 9:0 Hz), 7.72 (1H, dd, J ¼ 2:0, 9.0 Hz),
8.03 (1H, d, J ¼ 2:0 Hz), 11.3 (1H, broad s); HRMS:
calcd. for C11H11O4NClF3S, 345.0049; found, 345.0047.
Isopropyl 5-chloro-2-[(trifluoromethyl)sulfonyl]ami-
nobenzoate (4b): 20%; mp 41.9ꢁC; NMR (250 MHz)
ꢀH (CDCl3): 1.42 (3H, d, J ¼ 6:2 Hz), 5.30 (1H, m), 7.52
(1H, dd, J ¼ 2:5, 9.2 Hz), 7.73 (1H, d, J ¼ 9:2 Hz), 8.02
(1H, d, J ¼ 2:5 Hz), 11.2 (1H, broad s).
Dosage (g/m2)–Activity (%) after 24 hours
Compound
0.08 (g/m2)
1b
2b
3b
4b
5b
6b
8b
9b
+++
+++
+++
+++
+
+++
+++
+++
n-Butyl 5-chloro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (5b): 20%; nD (24.0), 1.4932; NMR (400 MHz)
ꢀH (CDCl3): 1.00 (3H, t, J ¼ 7:6 Hz), 1.47 (2H, m), 1.80
(2H, m), 4.39 (2H, m), 7.52 (1H, d, J ¼ 9:0 Hz), 7.72
(1H, d, J ¼ 9:0 Hz), 8.02 (1H, s), 11.3 (1H, broad s);
HRMS: calcd. for C12H13O4NClF3S, 359.0206; found,
359.0220.
Test: filter paper contact method
+++ 100% mortality, ++ >90% mortality,
+ 70–90% mortality,
— almost the same as untreated sample.
alkyl showed higher activity in comparison with a
bulkier phenoxy carbonyl group. The activity against
Chelacarops moorei (Cm) was particularly strong with
an alkoxycarbonly group having a C1-C3 alkyl.
Compounds 1b–4b, 6b, 8b and 9b completely con-
trolled Dermatophagoides farinae (Df) and Tyrophagus
putrescentiae (Tp), as well as Chelacarops moorei (Cm)
(Tables 1 and 2).
t-Butyl 5-chloro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (6b): 14%; mp 87.6ꢁC; NMR (400 MHz) ꢀH
(CDCl3): 1.63 (9H, s), 7.51 (1H, dd, J ¼ 2:7, 9.0 Hz),
7.72 (1H, d, J ¼ 9:0 Hz), 7.94 (1H, d, J ¼ 2:7 Hz), 11.4
(1H, broad s); HRMS: calcd. for C12H13O4NClF3S,
316.0206; found, 359.0220.
Judging from these findings and the availability of the
necessary raw materials, compound 1b (methyl 5-
chloro-2-[(trifluoromethyl)sulfonyl]aminobenzoate) was
selected and has been developed as a new miticide for
house dust mites.
Phenyl 5-chloro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (7b): 14%; mp 117.4ꢁC; NMR (250 MHz) ꢀH
(CDCl3): 7.21 (1H, d, J ¼ 8:8 Hz), 7.32–7.64 (5H, m),
7.80 (1H, d, J ¼ 8:8 Hz), 8.30 (1H, s), 11.3 (1H, broad s).
Methyl 5-bromo-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (8b): 41%; mp 73.8ꢁC; NMR (400 MHz) ꢀH
(CDCl3): 4.01 (3H, s), 7.68 (2H, s), 8.20 (1H, s), 11.2
(1H, broad s); HRMS: calcd. for C9H7O4NBrF3S,
360.9231; found, 360.9258.
Experimental. Melting point (mp) data were deter-
mined with Yanagimoto micro melting point apparatus
and are uncorrected. Refractive indexes (nD) were
1
determined with Atago refractive index apparatus. H-
NMR spectra were measured with a Hitachi R-24B
spectrometer (60 MHz), JEOL EX-300 spectrometer
(300 MHz) or JEOL AL400 spectrometer (400 MHz).
Methyl 5-chloro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (1b). To a stirred solution of methyl 2-
amino-5-chlorobenzoate (1a, 3.8 g) and triethylamine
(3.2 g) in dry chloroform (50 ml) was added dropwise
trifluoromethanesulfonic anhydride (8.7 g) at below 5ꢁC.
After stirring at room temperature for 8 hrs, the resulting
mixture was poured into ice-cooled water and extracted
twice with chloroform. The organic layers were com-
bined, washed with water and then dried over anhydrous
sodium sulfate. Evaporation of the solvent gave a
residue which was chromatographed on silica gel with
chloroform as the eluent to give 1b, 3.8 g, 58%; mp
80.7ꢁC; NMR (250 MHz) ꢀH (CDCl3): 3.99 (3H, s), 7.53
(1H, dd, J ¼ 2:4, 9.1 Hz), 7.73 (1H, d, J ¼ 9:1 Hz), 8.05
(1H, d, J ¼ 2:4 Hz), 11.2 (1H, broad s); HRMS: calcd.
for C9H7O4NClF3S, 316.9736; found, 316.9737.
Methyl
5-iodo-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (9b): 34%; mp 61.2ꢁC; NMR (400 MHz) ꢀH
(CDCl3): 4.05 (3H, s), 7.52 (1H, m), 7.84 (1H, m), 8.37
(1H, d, J ¼ 2:2 Hz), 11.2 (1H, broad s); HRMS: calcd.
for C9H7O4NF3SI, 408.9093; found, 408.9115.
Methyl 5-methyl-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (10b): 33%; mp 57.8ꢁC; NMR (400 MHz) ꢀH
(CDCl3): 2.42 (3H, s), 4.02 (3H, s), 7.39 (1H, d,
J ¼ 8:8 Hz), 7.67 (1H, d, J ¼ 8:8 Hz), 7.87 (1H,s), 11.1
(1H, broad s); HRMS: calcd. for C10H10O4NClF3S,
297.0282; found, 297.0291.
Methyl 5-nitro-2-[(trifluoromethyl)sulfonyl]amino-
benzoate (11b): 20%; mp 89.5ꢁC; NMR (400 MHz) ꢀH
(CDCl3): 4.07 (3H, s), 7.97 (1H, d, J ¼ 9:3 Hz), 8.44
(1H, d, J ¼ 9:3 Hz), 8.98 (1H, s), 11.7 (1H, broad s).
Methyl 5-methoxy-2-[(trifluoromethyl)sulfonyl]ami-
nobenzoate (12b): 32%; nD (26.0), 1.4921; NMR
(400 MHz) ꢀH (CDCl3): 3.85 (3H, s), 4.01 (3H, s),
7.15 (1H, dd, J ¼ 2:9, 9.2 Hz), 7.54 (1H, d, J ¼ 2:9 Hz),
7.68 (1H, d, J ¼ 9:2 Hz), 10.8 (1H, broad s); HRMS:
calcd. for C10H10O5NF3S, 313.0232; found, 313.0244.
Methyl 5-trifluoromethyl-2-[(trifluoromethyl)sulfo-
nyl]amino benzoate (13b): 32%; nD (26.0), 1.4632;
NMR (400 MHz) ꢀH (CDCl3): 4.03 (3H, s), 7.83 (1H, d,
Compounds 2b–15b were prepared in a similar
manner. Ethyl 5-chloro-2-[(trifluoromethyl)sulfonyl]-
aminobenzoate (2b): 58%; mp 65.7ꢁC; NMR (60 MHz)
ꢀH (CDCl3): 1.42 (3H, t, J ¼ 7:2 Hz), 4.42 (2H, q,
J ¼ 7:2 Hz), 7.42 (1H, dd, J ¼ 2:2, 8.6 Hz), 7.73 (1H, d,