OXADIAZOLINE COMPOUND AND FORMULATION FOR CONTROLLING HARMFUL ORGANISMS

Abstract

The present invention provides a compound represented by formula (I) (in formula (I), R.sup.1 represents a substituted or unsubstituted C1-6 alkyl group, R.sup.2 represents a substituted or unsubstituted C1-8 alkyl group, R.sup.3 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group, A represents a substituted or unsubstituted o-phenylene group, a substituted or unsubstituted bezylene group, or the like, B represents an oxy group, a substituted or unsubstituted oxymethylene group, or the like, and Q represents a substituted or unsubstituted o-phenylene group), or a salt thereof.

##STR00001##

Claims

1. A compound represented by formula (I) or a salt thereof ##STR00084## [in formula (I), R.sup.1 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C6-10 aryl C1-6 alkyl group, or a substituted or unsubstituted C1-6 alkyl carbonyl group, R.sup.2 represents a substituted or unsubstituted C1-8 alkyl group, a substituted or unsubstituted C3-10 cycloalkyl group, a substituted or unsubstituted C6-10 aryl group, a substituted or unsubstituted C6-10 aryl C1-6 alkyl group, or a substituted or unsubstituted C1-6 alkoxy carbonyl group, R.sup.3 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C6-10 aryl C1-6 alkyl group, a substituted or unsubstituted C1-6 alkyl carbonyl group, or a substituted or unsubstituted C1-6 alkoxy carbonyl group, R.sup.2 and R.sup.3 may bind together to form a substituted or unsubstituted C3-5 alkylene group, A represents a substituted or unsubstituted o-phenylene group, a substituted or unsubstituted 5- to 6-membered heteroarylene group, a substituted or unsubstituted benzylene group, a substituted or unsubstituted dimethylene group, or a 1,2-cyclopropylene group, B represents a single bond, an oxy group, a substituted or unsubstituted oxymethylene group, a substituted or unsubstituted methyleneoxy group, a substituted or unsubstituted thiomethylene group, a substituted or unsubstituted methylenethio group, a substituted or unsubstituted methylene group, a substituted or unsubstituted dimethylene group, or a substituted or unsubstituted vinylene group, a thio group, a substituted or unsubstituted sulfonylmethylene group, a substituted or unsubstituted methylenesulfonyl group, a substituted or unsubstituted trimethylene group, a substituted or unsubstituted oxyethylene group, a substituted or unsubstituted ethyleneoxy group, a substituted or unsubstituted propenylene group, a substituted or unsubstituted oxymethyleneoxy group, a group represented by a formula: NR.sup.a, a group represented by a formula: CH.sub.2NR.sup.a, or a group represented by a formula: NR.sup.aCH.sub.2, R.sup.a represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group, and Q represents a substituted or unsubstituted o-phenylene group.]

2. The compound according to claim 1, wherein A is a substituted or unsubstituted o-phenylene group, and B is a substituted or unsubstituted oxymethylene group, a substituted or unsubstituted methyleneoxy group, a substituted or unsubstituted dimethylene group, or a substituted or unsubstituted vinylene group.

3. The compound according to claim 1, wherein A is a substituted or unsubstituted o-phenylene group, and B is a substituted or unsubstituted oxymethylene group, or a substituted or unsubstituted methyleneoxy group.

4. A formulation for controlling harmful organisms, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

5. An insecticidal or acaricidal formulation, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

6. A formulation for controlling ectoparasites, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

7. A formulation for controlling Thysanoptera insect pests, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

Description

EXAMPLES

Formulation Examples

[0391] Some examples of the formulations for controlling harmful organisms, insecticidal or acaricidal formulations, formulations for controlling Thysanoptera insect pests of the present invention are described below. The additives and the addition ratios are not limited to those in the formulation examples and can be modified over a wide range. The term part in the formulation examples indicates part by weight.

[0392] The formulation examples for agricultural and horticultural use and for paddy rice are described below.

Formulation Example 1: Wettable Powder

[0393] 40 parts of the oxadiazoline compound of the present invention, 53 parts of diatomaceous earth, 4 parts of a higher alcohol sulfuric ester, and 3 parts of an alkylnaphthalene sulfonic acid salt were uniformly mixed and finely pulverized to obtain a wettable powder including 40% of an active ingredient.

Formulation Example 2: Emulsion

[0394] 30 parts of the oxadiazoline compound of the present invention, 33 parts of xylene, 30 parts of dimethylformamide and 7 parts of a polyoxyethylene alkyl aryl ether were mixed and dissolved to obtain an emulsion including 30% of an active ingredient.

Formulation Example 3: Granules

[0395] 5 parts of the oxadiazoline compound of the present invention, 40 parts of talc, 38 parts of clay, 10 parts of bentonite and 7 parts of sodium alkylsulfate were uniformly mixed and finely pulverized, followed by granulating into a granular shape having a diameter of 0.5 to 1.0 mm to obtain granules containing 5% of an active ingredient.

Formulation Example 4: Granules

[0396] 5 parts of the oxadiazoline compound of the present invention, 73 parts of clay, 20 parts of bentonite, 1 part of sodium dioctyl sulfosuccinate and 1 part of potassium phosphate were thoroughly pulverized and mixed. Water was added thereto, and the mixture was kneaded well, followed by granulating and drying to obtain granules containing 5% of an active ingredient.

Formulation Example 5: Suspension

[0397] 10 parts of the oxadiazoline compound according to the present invention, 4 parts of polyoxyethylene alkyl allyl ether, 2 parts of sodium polycarboxylate, 10 parts of glycerol, 0.2 parts of xanthan gum and 73.8 parts of water were mixed and wet-pulverized so as to have a grain size of 3 microns or less. Thereby, a suspension containing 10% of an active ingredient was obtained.

[0398] The formulation examples of the formulation for controlling ectoparasites are described below.

Formulation Example 6: Granulated Powder

[0399] 5 parts of the oxadiazoline compound of the present invention was dissolved in an organic solvent to obtain a solution. The solution mentioned above was sprayed on 94 parts of kaolin and 1 part of white carbon, followed by evaporating the solvent under reduced pressure. This type of granulated powder may be mixed with animal food.

Formulation Example 7: Impregnating Formulation

[0400] 0.1 to 1 part of the oxadiazoline compound of the present invention and 99 to 99.9 parts of peanut oil were uniformly mixed, and then filter-sterilized by means of a sterilizing filter.

Formulation Example 8: Pour-on Formulation

[0401] 5 parts of the oxadiazoline compound of the present invention, 10 parts of a myristic ester and 85 parts of isopropanol were uniformly mixed to obtain a pour-on formulation.

Formulation Example 9: Spot-on Formulation

[0402] 10 to 15 parts of the oxadiazoline compound of the present invention, 10 parts of a palmitic ester and 75 to 80 parts of isopropanol were uniformly mixed to obtain a spot-on formulation.

Formulation Example 10: Spray Formulation

[0403] 1 part of the oxadiazoline compound of the present invention, 10 parts of propylene glycol and 89 parts of isopropanol were uniformly mixed to obtain a spray formulation.

[0404] Next, Examples of compounds are described to explain the present invention more specifically. It should be understood that the present invention is not limited to the following examples of compounds.

Reference Example 1

Synthesis of 1-(tert-butyl)-3-(6,11-dihydrodibenzo[b,e]oxepin-11-yl)thiourea

[0405] ##STR00007##

[0406] 6,11-Dihydrodibenzo[b,e]oxepin-11-ol was synthesized in accordance with the method described in Chemical and Pharmaceutical Bulletin, 1991, 39, 0, 2564.

[0407] 6,11-Dihydrodibenzo[b,e]oxepin-11-ol (4.2 g) was dissolved in dichloromethane (100 mL), and subsequently, 1-(t-butyl)thiourea (2.8 g) and aluminum trifluoromethane sulfonate (0.10 g) were added thereto. The mixture was stirred for 25 hours. Subsequently, the reaction solvent was distilled off. Subsequently, the residue was purified by column chromatography with silica gel. Thereby, 6.1 g of the objective product was obtained.

[0408] Melting point: 167-168 C.

Reference Example 2

Synthesis of N-tert-butyl-N-(6,11-dihydrodibenzo[b,e]oxepin-11-yl) methanediimine

[0409] ##STR00008##

[0410] Triethylamine (6.8 ml) and 2-chloro-1-methylpyridinium iodide (6.3 g) were added to a solution of the thiourea (6.7 g) obtained in Reference Example 1 dissolved in acetonitrile (54 ml), and the mixture was stirred for 4 hours at room temperature. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography with silica gel. Thereby, 4.7 g of the objective product was obtained.

[0411] .sup.1H-NMR (CDCl.sub.3) ppm: 1.06 (s, 9H), 4.94 (d, 1H), 5.51 (s, 1H), 5.87 (d, 1H), 6.90 (m, 2H), 7.20 (m, 1H), 7.33 (m, 5H).

Example 1

Synthesis of N-(tert-butyl)-2-methyl-2H,6H-spiro[dibenzo[b,e]oxepine-11,5-[1,2,4]oxadiazol]-3-amine (Compound No. a-11)

[0412] ##STR00009##

[0413] N-Methylhydroxyamine hydrochloride (1.6 g) and triethylamine (2.6 ml) were added to a solution of carbodiimide (4.7 g) obtained in Reference Example 2 dissolved in acetonitrile (53 ml), and the mixture was stirred for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, and subsequently, dichloromethane (80 ml) and manganese dioxide (1.4 g) were added thereto. The mixture was stirred for 4 hours at room temperature. The reaction solution was filtered with celite. The insoluble material was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude product was washed with hexane. Thereby, 4.6 g of the objective product was obtained.

[0414] .sup.1H-NMR (CDCl.sub.3) ppm: 1.58 (s, 9H), 2.82 (s, 3H), 3.78 (s, 1H), 5.05 (d, 1H), 6.02 (d, 1H), 6.83 (d, 1H), 6.90 (t, 1H), 7.18 (t, 1H), 7.28 (m, 3H), 7.77 (m, 2H).

Example 2

Synthesis of N-(tert-butyl)-N-ethyl-2-methyl-2H,6H-spiro [dibenzo[b,e]oxepine-11,5-[1,2,4]oxadiazol]-3-amine (Compound No. a-10)

[0415] ##STR00010##

[0416] Sodium hydride (0.8 g) was added to a solution of the amine (4.6 g) obtained in Example 1 dissolved in DMF (45 ml) at 0 C., and the mixture was stirred for 30 minutes. Ethyl iodide (2.1 ml) was added thereto, and the mixture was stirred for 3 hours at 0 C. The reaction solution was added to water with ice. The mixture was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Subsequently, the filtrate was concentrated under reduced pressure. The obtained crude product was purified by column chromatography with silica gel. Thereby, 2.5 g of the objective product was obtained.

[0417] .sup.1H-NMR (CDCl.sub.3) ppm: 1.17 (t, 3H), 1.62 (s, 9H), 2.78 (s, 3H), 3.36 (q, 2H), 5.12 (d, 1H), 6.02 (d, 1H), 6.85 (m, 2H), 7.19 (t, 1H), 7.28 (m, 3H), 7.77 (m, 2H).

Reference Example 3

Synthesis of 1-(tert-butyl)-3-(10,11-dihydrodibenzo[b,f]oxepin-10-yl)thiourea

[0418] ##STR00011##

[0419] 10,11-Dihydro-dibenz[b,f]oxepin-10-ylamine was synthesized in accordance with the method described in Angewandte ChemieInternational Edition, 2015, 54, 17, 5049.

[0420] 10,11-Dihydro-dibenz[b,f]oxepin-10-ylamine (0.59 g) was dissolved in tetrahydrofuran (10 ml), and subsequently, t-butyl isothiocyanate (0.55 g) was added thereto. The mixture was stirred for 17 hours at room temperature, and subsequently, the solvent was distilled off therefrom. The residue was purified by column chromatography with silica gel. Thereby, 0.10 g of the objective product was obtained.

Example 3

Synthesis of N-(tert-butyl)-2-methyl-2H, 11H-spiro[dibenzo[b,f]oxepine-10,5-[1,2,4]oxadiazol]-3-amine (Compound No. a-22)

[0421] ##STR00012##

[0422] The thiourea (0.10 g) obtained in Reference Example 3 was dissolved in acetonitrile (3 ml). Subsequently, triethylamine (88 mg) and 2-chloro-1-methylpyridinium iodide (0.11 g) were added thereto, and the mixture was stirred for 4 hours at room temperature. N-methylhydroxyamine hydrochloride (48 mg) and triethylamine (58 mg) were added to the reaction solution, and the mixture was stirred for 18 hours at room temperature. The reaction solution was concentrated under reduced pressure. Subsequently, the residue was purified by column chromatography with silica gel. Thereby, 0.06 g of the objective product was obtained.

Reference Example 4

Synthesis of 2-methyl-2H,6H-spiro[dibenzo[b,e]oxepine-11,5-[1,2,4]oxadiazol]-3-amine

[0423] ##STR00013##

[0424] Dibenzo[b,e]oxepin-11(6H)-one (3.2 g) was dissolved in dichloromethane (30 ml), and subsequently, titanium tetrachloride (5.7 g) was added thereto. N,N-bis(trimethylsilyl)carbodiimide (5.6 g) was dropwise added thereto, and subsequently, the mixture was stirred for one hour at room temperature. Subsequently, water was added thereto to quench the reaction. The organic layer of the reaction mixture was extracted with dichloromethane, and the solvent thereof was distilled off under reduced pressure. The obtained crude product was dissolved in tetrahydrofuran (30 ml). Subsequently, N-hydroxyamine hydrochloride (2.5 g) and triethylamine (3.0 g) were added thereto, and the mixture was stirred for one hour at 60 C. The solid material was removed therefrom by filtration. Subsequently, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography with silica gel. Thereby, 2.9 g of the objective product was obtained.

[0425] .sup.1H-NMR (CDCl.sub.3) ppm: 2.98 (s, 3H), 5.22 (d, 1H), 5.82 (d, 1H), 6.87 (d, 1H), 6.94 (m, 1H), 7.24-7.30 (m, 4H), 7.76-7.82 (m, 2H).

Example 4

Synthesis of N-(tert-butyl)-2-methyl-2H,6H-spiro[dibenzo[b,e]oxepine-11,5-[1,2,4]oxadiazol]-3-amine (Compound No. a-11)

[0426] ##STR00014##

[0427] t-Butyl 2,2,2-trichloroacetimidate (0.13 ml) and boron trifluoride ethyl ether complex (46 l) were added to a solution of the amine (0.1 g) obtained in Reference Example 4 dissolved in 1,2-dichloroethane (1.8 ml), and the mixture was stirred for 2 hours under refluxing by heating. The reaction solution was added to a saturated aqueous solution of sodium hydrogen carbonate, and the mixture was subjected to extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and filtered. Subsequently, the filtrate was concentrated under reduced pressure. The obtained crude product was purified by column chromatography with silica gel. Thereby, 2.5 mg (yield 2%) of the objective product was obtained.

[0428] .sup.1H-NMR (CDCl.sub.3) ppm: 1.58 (s, 9H), 2.82 (s, 3H), 3.78 (s, 1H), 5.05 (d, 1H), 6.02 (d, 1H), 6.83 (d, 1H), 6.90 (t, 1H), 7.18 (t, 1H), 7.28 (m, 3H), 7.77 (m, 2H).

Reference Example 5

Synthesis of 1-(tert-butyl)-3-(6-fluoro-2,2-dimethylchroman-4-yl)thiourea

[0429] ##STR00015##

[0430] t-Butyl isothiocyanate (1.9 g) was added to a solution of 6-fluoro-2,2-dimethylchroman-4-amine (3.2 g) dissolved in dichloromethane (54 ml), and the mixture was stirred for 6 hours under refluxing by heating. The reaction solution was concentrated. The obtained solid was washed with ether. Thereby, 3.9 g of the objective product was obtained.

Reference Example 6

Synthesis of 2-(tert-butyl)-3-(6-fluoro-2,2-dimethylchroman-4-yl)-1-hydroxy-1-methylguanidine

[0431] ##STR00016##

[0432] Triethylamine (2.0 ml) and 2-chloro-1-methylpyridinium iodide (1.8 g) were added to a solution of the thiourea (1.84 g) obtained in Reference Example 5 dissolved in acetonitrile (20 ml), and the mixture was stirred for 18 hours at room temperature. N-methylhydroxyamine hydrochloride (0.6 g) and pyridine (1.2 ml) were added to the reaction solution, and the mixture was stirred for 14 hours at room temperature. The reaction solution was added to water, and the mixture was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Subsequently, the filtrate was concentrated under reduced pressure. The obtained crude product was purified by column chromatography with silica gel. Thereby, 0.4 g of the objective product was obtained.

Example 5

Synthesis of N-(tert-butyl)-6-fluoro-2,2,2-trimethyl-2H-spiro [chromane-4,5-[1,2,4]oxadiazol]-3-amine (Compound No. a-20)

[0433] ##STR00017##

[0434] Manganese dioxide (0.4 g) was added to a solution of guanidine (0.4 g) obtained in Reference Example 6 dissolved in chloroform (10 ml), and the mixture was stirred for 3 days at room temperature. The reaction solution was filtered with celite, and the insoluble material was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The obtained crude product was purified by column chromatography with silica gel. Thereby, 0.15 g of the objective product was obtained.

[0435] Some of the oxadiazoline compounds according to the present invention (Compound Nos. a-1 to a-43) which were produced by the same methods as those described in the Examples mentioned above are shown below together with the physical properties (melting point or NMR).

##STR00018##

[0436] m.p. 95-96 C.

##STR00019##

[0437] m.p. 113-114 C.

##STR00020##

[0438] m.p. 154-156 C.

##STR00021##

[0439] m.p. 130-132 C.

##STR00022##

[0440] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.67 (s, 9H), 2.80 (s, 3H), 3.24 (s, 3H), 4.69 (d, 2H), 5.15 (d, 1H), 5.99 (d, 1H), 6.82-6.88 (m, 2H), 7.18 (m, 1H), 7.25-7.30 (m, 3H), 7.73 (m, 1H).

##STR00023##

[0441] m.p. 175-177 C.

##STR00024##

[0442] m.p.: 148-150 C.

##STR00025##

[0443] m.p.: 163-166 C.

##STR00026##

[0444] m.p.: 181-183 C.

##STR00027##

[0445] m.p.: 85-86 C.

##STR00028##

[0446] m.p.: 196-198 C.

##STR00029##

[0447] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.13 (t, 3H), 1.52 (s, 9H), 2.75 (s, 3H), 3.10 (m, 2H), 3.32 (q, 2H), 3.69 (m, 2H), 7.09-7.13 (m, 6H), 7.78-7.81 (m, 2H).

##STR00030##

[0448] m.p.: 130-131 C.

##STR00031##

[0449] m.p.: 68-71 C.

##STR00032##

[0450] m.p.: 149-151 C.

##STR00033##

[0451] m.p.: 168-170 C.

##STR00034##

m.p.: 144-146 C.

[0452] ##STR00035##

[0453] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.09 (t, 3H), 1.63 (s, 9H), 2.49 (s, 3H), 3.27 (q, 2H), 7.10 (s, 2H), 7.35 (m, 6H), 7.97 (d, 2H).

##STR00036##

[0454] m.p.: 156-158 C.

##STR00037##

[0455] m.p.: 94-97 C.

##STR00038##

[0456] m.p.: 94.8-97.5 C.

##STR00039##

[0457] m.p.: 132-135 C.

##STR00040##

[0458] m.p.: 122-124 C.

##STR00041##

[0459] m.p.: 82-84 C.

##STR00042##

[0460] m.p.: 118-120 C.

##STR00043##

[0461] m.p.: 85-87 C.

##STR00044##

[0462] m.p.: 100-102 C.

##STR00045##

[0463] m.p. 143-145 C.

##STR00046##

[0464] m.p.: 151-153 C.

##STR00047##

[0465] m.p.: 107-109 C.

##STR00048##

[0466] m.p.: 142-143 C.

##STR00049##

[0467] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.40 (s, 9H), 3.02 (s, 3H), 3.27 (d, 1H), 3.40 (s, 3H), 3.56 (d, 1H), 6.91 (t, 1H), 7.01 (m, 1H), 7.08-7.25 (m, 5H), 7.42 (d, 1H).

##STR00050##

[0468] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.40 (s, 9H), 3.04 (s, 3H), 3.72 (d, 1H), 3.84 (d, 1H), 7.09-7.15 (m, 3H), 7.19 (m, 1H), 7.32 (d, 1H), 7.41 (d, 1H), 7.48-7.53 (m, 2H).

##STR00051##

[0469] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.40 (s, 9H), 2.89 (s, 3H), 3.07 (s, 3H), 3.35 (d, 1H), 3.40 (s, 3H), 3.55 (d, 1H), 6.92 (t, 1H), 7.01-7.25 (m, 6H), 7.42 (d, 1H).

##STR00052##

[0470] m.p.: 94-96 C.

##STR00053##

[0471] m.p.: 153-155 C.

##STR00054##

[0472] m.p.: 141-143 C.

##STR00055##

[0473] m.p.: 75-77 C.

##STR00056##

[0474] m.p.: 149-151 C.

##STR00057##

[0475] m.p.: 67-69 C.

##STR00058##

[0476] m.p.: 148-150 C.

##STR00059##

[0477] m.p.: 159-161 C.

##STR00060##

[0478] m.p.: 133-135 C.

[0479] In addition, among the oxadiazoline compounds according to the present invention, some compounds represented by formula (II-a) are shown in Table 1, together with the physical properties (melting point, refractive index, or characteristic state).

[0480] In Table 1, Me represents a methyl group, Et represents an ethyl group, n-Pr represents an n-propyl group, t-Bu represents a t-butyl group, Bn represents a benzyl group, Ac represents an acetyl group, BOC represents a t-butoxycarbonyl group, Ph represents a phenyl group, and c-Pr represents a cyclopropyl group.

##STR00061##

TABLE-US-00001 TABLE 1 Compound Physical No. R.sup.1 R.sup.2 R.sup.3 (X.sup.q)m (X.sup.a)n property b-1 Me t-Bu H 2-F m.p. 195-198 C. b-2 Me t-Bu Et 2-F m.p. 105-107 C. b-3 Me t-Bu H 4-F m.p. 175-177 C. b-4 Me t-Bu Et 4-F m.p. 102-104 C. b-5 Me t-Bu H 2-Cl m.p. 171-173 C. b-6 Me t-Bu Et 2-Cl m.p. 68-70 C. b-7 Me t-Bu H 2-MeO m.p. 145-146 C. b-8 Me t-Bu Et 2-MeO m.p. 76-78 C. b-9 Me t-Bu H 3-F m.p. 146-148 C. b-10 Me t-Bu Et 3-F m.p. 90-92 C. b-11 Me t-Bu H 3-Cl m.p. 135-137 C. b-12 Me t-Bu Et 3-Cl m.p. 99-101 C. b-13 Me t-Bu H 2-CF.sub.3O m.p. 117-119 C. b-14 Me t-Bu H 3-CF.sub.3O m.p. 138-140 C. b-15 Me t-Bu H 8-Cl m.p. 174-176 C. b-16 Me t-Bu H 1,2-F.sub.2 m.p. 160-163 C. b-17 Me t-Bu H 2-Et m.p. 142-144 C. b-18 Me BOC BOC m.p. 150-152 C. b-19 Me BOC H m.p. 194-196 C. b-20 Me t-Bu H 3-Ph m.p. 183-185 C. b-21 Me t-Bu H 3-(c-Pr) m.p. 78-80 C. b-22 Me t-Bu H 2-MeS amorphous b-23 Me t-Bu H 2-MeOC(O)CH.sub.2 m.p. 120-122 C. b-24 Me t-Bu H 3-CN m.p. 96-98 C. b-25 Et t-Bu H m.p. 188-190 C. b-26 Et t-Bu Me m.p. 112-114 C. b-27 Et t-Bu Et amorphous b-28 Me t-Bu Et 3-CF.sub.3CH.sub.2O amorphous b-29 Me t-Bu H 3-Br m.p. 144-146 C. b-30 Me t-Bu Et 3-Br amorphous b-31 Me t-Bu H 4-Br m.p. 192-194 C. b-32 Me t-Bu H 4-Me m.p. 168-170 C. b-33 Me t-Bu H 4-Ph amorphous b-34 Me t-Bu H 3-MeS m.p. 80-82 C. b-35 Me t-Bu Et 3-MeS amorphous b-36 allyl t-Bu H m.p. 148-150 C. b-37 H t-Bu H m.p. 200 C. up b-38 Me t-Bu H 4-CN m.p. 179-181 C. b-39 Me t-Bu H 4-Cl m.p. 188-191 C. b-40 Me t-Bu Et 3-MeS(O) amorphous b-41 allyl t-Bu Me m.p. 72-74 C. b-42 allyl t-Bu Et nD(20.9) 1.6231 b-43 H t-Bu Me m.p. 43-45 C. b-44 H t-Bu Et nD(20.8) 1.5831 b-45 Me t-Bu H 2,4-Me.sub.2 m.p. 196-198 C. b-46 Me t-Bu Me 2,4-Me.sub.2 m.p. 130-132 C. b-47 Me t-Bu Et 2,4-Me.sub.2 m.p. 143-145 C. b-48 Me t-Bu Me m.p. 122-124 C. b-49 Me t-Bu Bn m.p. 153-155 C. b-50 Me t-Bu Me 3-CF.sub.3O amorphous b-51 Me t-Bu Et 3-CF.sub.3O amorphous b-52 Me t-Bu Et 7-Cl m.p. 110-112 C. b-53 Me t-Bu Me 8-F m.p. 118-119 C. b-54 Me t-Bu Et 8-F m.p. 107-109 C. b-55 Me t-Bu Me 2-Me m.p. 108-110 C. b-56 Me t-Bu Et 2-Me amorphous b-57 Me t-Bu H 3-F m.p. 142-144 C. b-58 Me t-Bu allyl amorphous b-59 Me t-Bu n-Pr amorphous b-60 Me Me Me m.p. 150-154 C. b-61 Me t-Bu H 2-Br m.p. 148-151 C. b-62 Me t-Bu H 2-Ph m.p. 175-177 C. b-63 Me t-Bu H 2-MeOC(O) amorphous b-64 Me t-Bu H 2-CN m.p. 204-206 C. b-65 Me CH.sub.2CH.sub.2CH.sub.2CH.sub.2 m.p. 171-173 C. b-66 Bn t-Bu H m.p. 214-216 C. b-67 Ac t-Bu Me amorphous b-68 Me C(Me).sub.2Et H m.p. 140-142 C. b-69 Me C(Me).sub.2Et Me m.p. 136-138 C. b-70 Me C(Me).sub.2Et Et viscous oil b-71 Me 1-Me-c-Pr H m.p. 160-162 C. b-72 Me C(Me).sub.2CF.sub.3 H m.p. 166-168 C. b-73 Me C(Me).sub.2CF.sub.3 Me nD(21.9) 1.6192 b-74 Me t-Bu EtOCH.sub.2 nD(21.8) 1.6391 b-75 Me t-Bu MeOCH.sub.2CH.sub.2OCH.sub.2 nD(21.8) 1.6411 b-76 Me 4-CF.sub.3OPh H amorphous b-77 Me 4-ClPh H amorphous b-78 Me t-Bu Me 3-F m.p. 110-112 C. b-79 Me t-Bu t-Bu m.p. 150-152 C. b-80 Me t-Bu MeOCO m.p. 128-130 C. b-81 Me t-Bu Me 4-F m.p. 166-167 C. b-82 Me t-Bu H 1,3-F.sub.2 m.p. 114-116 C. b-83 Me t-Bu Et 1,3-F.sub.2 amorphous b-84 Me t-Bu H 3,4-F.sub.2 m.p. 152-154 C. b-85 Me t-Bu Me 3,4-F.sub.2 m.p. 135-136 C. b-86 Me t-Bu Et 3,4-F.sub.2 m.p. 102-104 C. b-87 Me t-Bu MeSCH.sub.2 nD(21.3) 1.6314 b-88 Me i-Pr H m.p. 178-180 C. b-89 Me i-Pr Me m.p. 165-167 C. b-90 Me i-Pr Et m.p. 103-105 C. b-91 Me i-Pr MeOCH.sub.2 nD(21.4) 1.6219 b-92 Me t-Bu Me 4-Cl m.p. 161-163 C. b-93 Me t-Bu Et 4-Cl m.p. 97-99 C. b-94 Me t-Bu Me 4-Br m.p. 148-150 C. b-95 Me t-Bu Et 4-Br amorphous b-96 Me t-Bu Me 4-Me m.p. 150-152 C. b-97 Me t-Bu Et 4-Me amorphous b-98 Me t-Bu H 7-F m.p. 168-170 C. b-99 Me t-Bu H 4-F 7-F m.p. 189-191 C. b-100 Me t-Bu Me 7-F m.p. 136-138 C. b-101 Me t-Bu Me 4-F 7-F m.p. 148-150 C. b-102 Me t-Bu Et 7-F m.p. 108-110 C. b-103 Me t-Bu Et 4-F 7-F nD(21.1) 1.6192 b-104 Me t-Bu MeOCH.sub.2 7-F nD(21.2) 1.6322 b-105 Me t-Bu MeOCH.sub.2 4-F 7-F nD(21.1) 1.6387 b-106 Me t-Bu Me 4-Vinyl m.p. 107-110 C. b-107 Me t-Bu Me 4-Et amorphous b-108 Me t-Bu Propargyl 4-F nD(20.4) 1.6128 b-109 Me t-Bu Et 3-Et amorphous b-110 Me t-Bu H 3-MeO amorphous b-111 Me t-Bu Me 3-MeO amorphous b-112 Me t-Bu Et 3-MeO amorphous b-113 Me t-Bu H 4-MeO m.p. 194-196 C. b-114 Me t-Bu Me 4-MeO m.p. 183-185 C. b-115 Me t-Bu Et 4-MeO m.p. 55-57 C. b-116 Me t-Bu MeOCH.sub.2 4-MeO nD(21.1) 1.6187 b-117 Me t-Bu n-Pr 4-F nD(20.8) 1.6042 b-118 Me t-Bu n-Pr 7-F m.p. 96-98 C. b-119 Me t-Bu H 7-Br m.p. 196-198 C. b-120 Me t-Bu Me 7-Br nD(20.9) 1.6151 b-121 Me t-Bu Et 7-Br nD(20.9) 1.6204 b-122 Me t-Bu H 7-Me m.p. 200-202 C. b-123 Me t-Bu Me 7-Me m.p. 120-122 C. b-124 Me t-Bu Et 7-Me nD(21.1) 1.6198 b-125 Me t-Bu H 7-Et m.p. 172-174 C. b-126 Me t-Bu Me 7-Et nD(21.1) 1.6231 b-127 Me t-Bu Et 7-Et nD(21) 1.6291 b-128 Me t-Bu H 7-Vinyl m.p. 195-197 C. b-129 Me t-Bu Me 7-Vinyl nD(21.3) 1.6135 b-130 Me t-Bu Et 7-Vinyl nD(21.2) 1.6187 b-131 Me t-Bu H 10-F m.p. 144-146 C. b-132 Me t-Bu Me 10-F m.p. 116-118 C. b-133 Me t-Bu Et 10-F nD(20.1) 1.6142 b-134 Me t-Bu n-Pr 10-F m.p. 97-99 C. b-135 Me C(Me).sub.2Et H 4-F m.p. 121-122 C. b-136 Me C(Me).sub.2Et H 4-Me m.p. 119-120 C. b-137 Me t-Bu Me 3-Me m.p. 58-60 C. b-138 Me t-Bu Et 3-Me amorphous b-139 Me t-Bu n-Pr 3-Me amorphous b-140 Me C(Me).sub.2Et Me 4-F m.p. 109-111 C. b-141 Me C(Me).sub.2Et Et 4-F amorphous b-142 Me C(Me).sub.2Et Me 4-Me m.p. 115-117 C. b-143 Me C(Me).sub.2Et Et 4-Me amorphous b-144 Me C(Et).sub.2Me H m.p. 52-54 C. b-145 Me C(Me).sub.2Ph H m.p. 197-198 C. b-146 Me C(Me).sub.2CH.sub.2(t-Bu) H m.p. 136-137 C. b-147 Me C(Me).sub.2(nPr) H m.p. 142-144 C. b-148 Me C(Me).sub.2CH.sub.2(t-Bu) Me m.p. 116-117 C. b-149 Me C(Me).sub.2CH.sub.2(t-Bu) Et amorphous b-150 Me C(Me).sub.2Ph Me m.p. 167-168 C. b-151 Me C(Me).sub.2Ph Et m.p. 160-161 C. b-152 Me C(Me).sub.2Ph n-Pr m.p. 154-155 C. b-153 Me C(Et).sub.2Me Me nD(21.9) 1.6031 b-154 Me C(Et).sub.2Me Et nD(21.9) 1.6124 b-155 Me C(Et).sub.2Me n-Pr nD(21.9) 1.6193 b-156 Me C(Me).sub.2(n-Pr) Me nD(22.1) 1.6138 b-157 Me C(Me).sub.2(n-Pr) Et m.p. 85-87 C. b-158 Me C(Me).sub.2(n-Pr) n-Pr nD(22) 1.6211 b-159 Me t-Bu H 4-Et m.p. 152-153 C. b-160 Me C(Me).sub.2Et H 4-Et m.p. 142-143 C. b-161 Me t-Bu Me 2-Cl m.p. 125-127 C. b-162 Me C(Me).sub.2Et Me 2-Cl m.p. 112-114 C. b-163 Me C(Me).sub.2Et Et 2-Cl amorphous b-164 Me C(Me).sub.2Et H 2-Cl m.p. 169-171 C. b-165 Me t-Bu Et 4-Et amorphous b-166 Me C(Me).sub.2Et Me 4-Et m.p. 73-75 C. b-167 Me C(Me).sub.2Et Et 4-Et amorphous b-168 Me C(Me).sub.2Et H 8-F m.p. 137-138 C. b-169 Me C(Me).sub.2Et H 3-F 8-F amorphous b-170 Me C(Me).sub.2Et H 3-Me m.p. 74-76 C. b-171 Me C(Me).sub.2(n-Pr) H 3-Me m.p. 60-62 C. b-172 Me C(Me).sub.2Et H 3-Cl m.p. 139-141 C. b-173 Me C(Me).sub.2(n-Pr) H 3-Cl m.p. 116-118 C. b-174 Me C(Me).sub.2Et Me 3-Me amorphous b-175 Me C(Me).sub.2(n-Pr) Me 3-Me amorphous b-176 Me C(Me).sub.2Et Et 3-Me amorphous b-177 Me C(Me).sub.2(n-Pr) Et 3-Cl m.p. 90-92 C. b-178 Me C(Me).sub.2Et Me 3-Me amorphous b-179 Me C(Me).sub.2(n-Pr) Me 3-Cl amorphous b-180 Me C(Me).sub.2Et Et 3-Cl amorphous b-181 Me C(Me).sub.2Et H 3-F m.p. 135-137 C. b-182 Me C(Me).sub.2Et Me 3-F m.p. 69-71 C. b-183 Me t-Bu H 4-(n-Pr) m.p. 133-135 C. b-184 Me t-Bu H 4-(n-Bu) m.p. 104-106 C. b-185 Me C(Me).sub.2Et Et 3-F nD(22.1) 1.6014 b-186 Me C(Me).sub.2Et n-Pr 3-F nD(22.2) 1.6219 b-187 Me C(Me).sub.2(n-Pr) H 3-F m.p. 111-113 C. b-188 Me C(Me).sub.2(n-Pr) Me 3-F nD(21.8) 1.6017 b-189 Me C(Me).sub.2(n-Pr) Et 3-F nD(22.3) 1.6113 b-190 Me C(Me).sub.2Et H 7-Cl m.p. 100-102 C. b-191 Me C(Me).sub.2Et Me 7-Cl m.p. 138-140 C. b-192 Me C(Me).sub.2Et Et 7-Cl nD(21.9) 1.5918 b-193 Me t-Bu H 3-Et m.p. 113-115 C. b-194 Me t-Bu Me 3-Et amorphous b-195 Me t-Bu Et 3-Et amorphous b-196 Me C(Me).sub.2Et H 7-F m.p. 132-134 C. b-197 Me C(Me).sub.2Et Me 7-F m.p. 140-142 C. b-198 Me C(Me).sub.2Et Et 7-F nD(20.5) 1.5536 b-199 Me C(Me).sub.2Et n-Pr 7-F nD(20.8) 1.5793

[0481] Among the compounds described above, with respect to the compounds which are in the form of an amorphous or a viscous oil, the NMR data thereof are shown below.

[0482] Compound No. (b-22): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.59 (s, 9H), 2.41 (s, 3H), 2.82 (s, 3H), 3.83 (s, 1H), 5.05 (d, 1H), 5.99 (d, 1H), 6.79 (d, 1H), 7.15 (d, 1H), 7.31 (m, 3H), 7.77 (m, 2H).

[0483] Compound No. (b-27): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.02 (t, 3H), 1.31 (t, 3H), 1.60 (s, 9H), 2.87 (q, 2H), 3.15 (q, 2H), 5.01 (d, 1H), 6.15 (d, 1H), 6.81 (m, 2H), 7.15 (dd, 1H), 7.27 (m, 3H), 7.72 (m, 2H).

[0484] Compound No. (b-28): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.17 (t, 3H), 1.62 (s, 9H), 2.77 (s, 3H), 3.35 (q, 2H), 4.24 (q, 2H), 5.10 (d, 1H), 6.05 (d, 1H), 6.37 (d, 1H), 6.50 (d, 1H), 7.27 (m, 3H), 7.72 (m, 2H).

[0485] Compound No. (b-30): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.17 (t, 3H), 1.59 (s, 9H), 2.78 (s, 3H), 3.37 (q, 2H), 5.18 (d, 1H), 6.00 (d, 1H), 7.20 (m, 2H), 7.29 (m, 2H), 7.47 (d, 1H), 7.72 (m, 2H).

[0486] Compound No. (b-33): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.59 (s, 9H), 2.85 (s, 3H), 3.82 (s, 1H), 4.98 (d, 1H), 5.84 (d, 1H), 7.00 (t, 1H), 7.12 (m, 1H), 7.29-7.40 (m, 8H), 7.81 (m, 2H).

[0487] Compound No. (b-35): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.16 (t, 3H), 1.61 (s, 9H), 2.40 (s, 3H), 2.81 (s, 3H), 3.32 (q, 2H), 5.05 (d, 1H), 6.01 (d, 1H), 6.70 (d, 1H), 6.80 (dd, 1H), 7.28 (m, 3H), 7.68 (d, 1H), 7.75 (dd, 1H).

[0488] Compound No. (b-40): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.18 (t, 3H), 1.59 (s, 9H), 2.60 (s, 3H), 2.82 (s, 3H), 3.38 (q, 2H), 5.23 (dd, 1H), 6.11 (dd, 1H), 7.04 (d, 1H), 7.18 (dd, 1H), 7.29 (m, 3H), 7.78 (d, 1H), 7.95 (dd, 1H).

[0489] Compound No. (b-50): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.59 (s, 9H), 2.74 (s, 3H), 2.90 (s, 3H), 5.11 (d, 1H), 6.07 (d, 1H), 6.68 (m, 2H), 7.30 (m, 3H), 7.72 (m, 1H), 7.80 (d, 1H).

[0490] Compound No. (b-51): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.15 (t, 3H), 1.60 (s, 9H), 2.77 (s, 3H), 3.35 (q, 2H), 5.15 (d, 1H), 6.06 (d, 1H), 6.70 (m, 2H), 7.30 (m, 3H), 7.72 (m, 1H), 7.79 (d, 1H).

[0491] Compound No. (b-56): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.15 (t, 3H), 1.61 (s, 9H), 2.20 (s, 3H), 2.79 (s, 3H), 3.35 (q, 2H), 5.15 (d, 1H), 5.96 (d, 1H), 6.73 (d, 1H), 6.96 (m, 1H), 7.28 (m, 3H), 7.56 (d, 1H), 7.73 (m, 1H).

[0492] Compound No. (b-58): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.61 (s, 9H), 2.77 (s, 3H), 3.96 (m, 2H), 5.11 (d, 2H), 5.19 (d, 1H), 5.90 (m, 1H), 6.03 (d, 1H), 6.83 (m, 2H), 7.18 (t, 1H), 7.25-7.30 (m, 3H), 7.73 (m, 2H).

[0493] Compound No. (b-59): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.81 (t, 3H), 1.58 (m, 2H), 1.61 (s, 9H), 2.77 (s, 3H), 3.21 (m, 2H), 5.13 (d, 1H), 6.03 (d, 1H), 6.83 (m, 2H), 7.18 (t, 1H), 7.25-7.30 (m, 3H), 7.73 (m, 2H).

[0494] Compound No. (b-63): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.61 (s, 9H), 2.84 (s, 3H), 3.82 (s, 3H), 5.15 (d, 1H), 6.11 (d, 1H), 6.84 (d, 1H), 7.30 (m, 3H), 7.73 (m, 1H), 7.82 (dd, 1H), 8.59 (d, 1H).

[0495] Compound No. (b-67): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.67 (s, 9H), 1.73 (s, 3H), 2.96 (s, 3H), 4.97 (d, 1H), 6.18 (d, 1H), 6.91 (m, 2H), 7.30 (m, 4H), 7.69 (d, 1H), 7.81 (d, 1H).

[0496] Compound (b-70): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.94 (t, 3H), 1.17 (t, 3H), 1.56 (m, 6H), 2.05 (q, 1H), 2.21 (q, 1H), 2.78 (s, 3H), 3.31 (q, 2H), 5.05 (d, 1H), 6.08 (d, 1H), 6.83 (m, 2H), 7.15 (t, 1H), 7.25 (t, 3H), 7.75 (m, 2H).

[0497] Compound (b-76): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 2.75 (s, 3H), 5.17 (d, 1H), 5.85 (d, 1H), 6.85 (m, 1H), 6.92 (m, 1H), 7.21-7.32 (m, 8H), 7.61 (m, 1H), 7.66 (m, 1H).

[0498] Compound (b-77): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 2.74 (s, 3H), 5.15 (d, 1H), 5.86 (d, 1H), 6.83 (m, 1H), 6.91 (m, 1H), 7.15-7.20 (m, 4H), 7.27-7.35 (m, 4H), 7.60 (m, 1H), 7.64 (m, 1H).

[0499] Compound (b-83): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.16 (t, 3H), 1.54 (s, 9H), 2.81 (s, 3H), 3.32 (q, 2H), 5.25 (d, 1H), 5.60 (d, 1H), 6.37-6.40 (m, 2H), 7.25 (m, 1H), 7.29-7.30 (m, 2H), 7.86 (m, 1H).

[0500] Compound (b-95): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.15 (t, 3H), 1.60 (s, 9H), 2.79 (s, 3H), 3.33 (q, 2H), 5.33 (d, 1H), 6.05 (d, 1H), 6.75 (t, 1H), 7.25-7.28 (m, 3H), 7.46 (m, 1H), 7.70-7.75 (m, 2H).

[0501] Compound (b-97): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.16 (t, 3H), 1.61 (s, 9H), 2.19 (s, 3H), 2.78 (s, 3H), 3.33 (q, 2H), 5.16 (d, 1H), 5.97 (d, 1H), 6.79 (t, 1H), 7.07 (m, 1H), 7.20-7.26 (m, 3H), 7.59 (m, 1H), 7.75 (m, 1H).

[0502] Compound (b-107): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.16 (t, 3H), 1.60 (s, 9H), 2.63 (m, 2H), 2.74 (s, 3H), 2.89 (s, 3H), 5.10 (d, 1H), 5.94 (d, 1H), 6.64 (t, 1H), 7.09 (m, 1H), 7.16-7.26 (m, 3H), 7.59 (m, 1H), 7.76 (m, 1H).

[0503] Compound (b-109): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.15-1.17 (m, 6H), 1.61 (s, 9H), 2.53 (q, 2H), 2.78 (s, 3H), 3.34 (q, 2H), 5.08 (d, 1H), 6.01 (d, 1H), 6.66 (s, 1H), 6.73 (d, 1H), 7.24-7.26 (m, 3H), 7.65 (d, 1H), 7.74 (m, 1H).

[0504] Compound (b-110): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.58 (s, 9H), 2.81 (s, 3H), 3.72 (s, 3H), 5.01 (d, 1H), 6.03 (d, 1H), 6.37 (d, 1H), 6.45 (m, 1H), 7.25-7.28 (m, 3H), 7.68-7.70 (m, 2H).

[0505] Compound (b-111): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.60 (s, 9H), 2.74 (s, 3H), 2.90 (s, 3H), 3.72 (s, 3H), 5.02 (d, 1H), 6.04 (d, 1H), 6.36 (d, 1H), 6.44 (m, 1H), 7.25-7.28 (m, 3H), 7.66 (d, 1H), 7.73 (m, 1H).

[0506] Compound (b-112): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.16 (t, 3H), 1.61 (s, 9H), 2.77 (s, 3H), 3.34 (q, 2H), 3.72 (s, 3H), 5.04 (d, 1H), 6.04 (d, 1H), 6.36 (d, 1H), 6.46 (m, 1H), 7.25-7.28 (m, 3H), 7.67 (d, 1H), 7.73 (m, 1H).

[0507] Compound (b-138): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.34 (t, 3H), 1.59 (s, 9H), 2.24 (s, 3H), 2.63 (m, 2H), 2.74 (s, 3H), 5.11 (d, 1H), 5.98 (d, 1H), 6.64 (t, 1H), 6.79 (m, 1H), 7.16-7.26 (m, 3H), 7.57 (m, 1H), 7.76 (m, 1H).

[0508] Compound (b-139): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.21 (t, 3H), 1.61 (s, 9H), 1.89 (m, 2H), 2.21 (s, 3H), 2.73 (m, 2H), 2.71 (s, 3H), 5.15 (d, 1H), 5.81 (d, 1H), 6.61 (d, 1H), 6.78 (m, 1H), 7.11-7.31 (m, 3H), 7.61 (m, 1H), 7.88 (m, 1H).

[0509] Compound (b-141): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.91 (t, 3H), 1.16 (t, 3H), 1.53 (s, 6H), 2.03 (m, 1H), 2.16 (m, 1H), 2.79 (s, 3H), 3.31 (m, 2H), 5.24 (d, 1H), 6.03 (d, 1H), 6.77 (m, 1H), 7.01 (m, 1H), 7.25-7.29 (m, 3H), 7.50 (m, 1H), 7.72 (m, 1H).

[0510] Compound (b-143): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.92 (t, 3H), 1.16 (t, 3H), 1.53 (s, 6H), 2.18 (s, 3H), 2.78 (s, 3H), 3.31 (q, 2H), 5.11 (d, 1H), 6.02 (d, 1H), 6.79 (t, 1H), 7.05 (m, 1H), 7.20-7.26 (m, 3H), 7.58 (m, 1H), 7.72 (m, 1H).

[0511] Compound (b-149): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.07 (s, 9H), 1.18 (t, 3H), 1.65 (s, 3H), 1.68 (s, 3H), 2.12 (d, 1H), 2.30 (d, 1H), 2.78 (s, 3H), 3.34 (q, 2H), 5.09 (d, 1H), 6.07 (d, 1H), 6.80-6.86 (m, 2H), 7.16 (m, 1H), 7.25-7.28 (m, 3H), 7.76-7.79 (m, 2H).

[0512] Compound (b-161): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.60 (s, 9H), 2.77 (s, 3H), 2.91 (s, 3H), 5.09 (d, 1H), 6.98 (d, 1H), 6.75 (d, 1H), 7.10 (m, 1H), 7.24-7.28 (m, 3H), 7.72-7.75 (m, 2H).

[0513] Compound (b-163): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.94 (t, 3H), 1.18 (t, 3H), 1.56 (m, 6H), 2.15 (m, 2H), 2.80 (s, 3H), 3.34 (q, 2H), 5.06 (d, 1H), 6.03 (d, 1H), 6.75 (d, 1H), 7.10 (m, 1H), 7.25-7.30 (m, 3H), 7.69-7.72 (m, 2H).

[0514] Compound (b-165): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 84-0310 1.15-1.18 (m, 6H), 1.61 (s, 9H), 2.61 (m, 2H), 2.77 (s, 3H), 3.33 (q, 2H), 5.14 (d, 1H), 5.95 (d, 1H), 6.84 (m, 1H), 7.08 (m, 1H), 7.21-7.26 (m, 3H), 7.60 (m, 1H), 7.75 (m, 1H).

[0515] Compound (b-167): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 84-0312 0.93 (t, 3H), 1.15-1.18 (m, 6H), 1.53 (s, 6H), 2.08 (m, 1H), 2.10 (m, 1H), 2.62 (m, 2H), 2.77 (s, 3H), 3.32 (q, 2H), 5.09 (d, 1H), 5.98 (d, 1H), 6.83 (t, 1H), 7.08 (m, 1H), 7.21-7.26 (m, 3H), 7.60 (m, 1H), 7.73 (m, 1H).

[0516] Compound (b-174): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.99 (t, 3H), 1.56 (s, 6H), 2.18 (q, 2H), 2.27 (s, 3H), 2.80 (s, 3H), 2.93 (s, 3H), 5.07 (d, 1H), 6.09 (d, 1H), 6.70 (s, 1H), 6.73 (d, 1H), 7.29 (m, 3H), 7.67 (d, 1H), 7.77 (m, 1H).

[0517] Compound (b-175): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.00 (t, 3H), 1.41 (m, 2H), 1.55 (s, 6H), 2.09 (q, 2H), 2.24 (s, 3H), 2.77 (s, 3H), 2.90 (s, 3H), 5.06 (d, 1H), 6.05 (d, 1H), 6.67 (s, 1H), 6.71 (d, 1H), 7.27 (m, 3H), 7.64 (d, 1H), 7.73 (m, 1H).

[0518] Compound (b-176): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.87 (t, 3H), 1.16 (t, 3H), 1.54 (s, 6H), 2.13 (m, 2H), 2.22 (s, 3H), 2.78 (s, 3H), 3.32 (m, 2H), 5.04 (d, 1H), 6.04 (d, 1H), 6.64 (s, 1H), 6.69 (d, 1H), 7.25 (m, 3H), 7.61 (d, 1H), 7.70 (m, 1H).

[0519] Compound (b-178): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.94 (t, 3H), 1.53 (s, 6H), 2.09-2.14 (m, 2H), 2.76 (s, 3H), 2.89 (s, 3H), 5.06 (d, 1H), 6.05 (d, 1H), 7.81-7.83 (m, 2H), 7.26 (m, 3H), 7.67-7.70 (m, 2H).

[0520] Compound (b-179): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.97 (t, 3H), 1.52 (s, 6H), 2.03-2.06 (m, 2H), 2.75 (s, 3H), 2.88 (s, 3H), 5.04 (d, 1H), 6.03 (d, 1H), 6.82 (m, 2H), 7.24-7.27 (m, 3H), 7.66-7.71 (m, 2H).

[0521] Compound (b-180): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.91 (t, 3H), 1.16 (t, 3H), 1.53 (s, 3H), 1.55 (s, 3H), 2.00-2.05 (m, 1H), 2.17-2.21 (m, 2H), 2.78 (s, 3H), 3.32 (q, 2H), 5.09 (d, 1H), 6.05 (d, 1H), 6.82-6.84 (m, 2H), 7.27 (m, 3H), 7.66-7.71 (m, 2H).

[0522] Compound (b-194): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.15 (t, 3H), 1.60 (s, 9H), 2.53 (q, 2H), 2.75 (s, 3H), 2.89 (s, 3H), 5.04 (d, 1H), 6.02 (d, 1H), 6.66 (s, 1H), 6.73 (d, 1H), 7.25 (m, 3H), 7.65 (d, 1H), 7.73 (m, 1H).

[0523] In addition, among the oxadiazoline compounds according to the present invention, some of the compounds represented by formula (II-b) are shown in Table 2, together with the physical properties (melting point, refractive index, or characteristic state).

[0524] In Table 2, Me represents a methyl group, Et represents an ethyl group, t-Bu represents a t-butyl group, Bn represents a benzyl group, and Ph represents a phenyl group.

##STR00062##

TABLE-US-00002 TABLE 2 Compound Physical No. R.sup.1 R.sup.2 R.sup.3 (X.sup.q)m B.sup.1 X.sup.b1 X.sup.b2 property c-1 Me t-Bu H 7-MeO CH.sub.2 H H m.p. 120-122 C. c-2 Me t-Bu H O Me Me m.p. 79-82 C. c-3 Me t-Bu H O H H m.p. 90-92 C. c-4 Me t-Bu H O CH.sub.2CH.sub.2CH.sub.2CH.sub.2 m.p. 102-104 C. c-5 Me t-Bu H 6-Cl O Me Me nD(23.3) 1.5269 c-6 Me t-Bu Et 6-Cl O Me Me nD(22.6) 1.5229 c-7 Me t-Bu H 6-Br O Me Me nD(22.8) 1.536 c-8 Me t-Bu H 6-Cl, 7-Me O Me Me nD(22.2) 1.5299 c-9 Me t-Bu H 6-F O Me Me m.p. 86-88 C. c-10 Me t-Bu H 6-F O H H m.p. 85-86 C. c-11 Me t-Bu H 7-MeO O Me Me m.p. 95-97 C. c-12 Me t-Bu H O Ph H m.p. 139-141 C. c-13 Me t-Bu H 6-Me O Me Me m.p. 104-107 C. c-14 Me t-Bu H O 4-ClPh H m.p. 155-156 C. c-15 Me t-Bu H O 4-FPh H m.p. 143-145 C. c-16 Me t-Bu H O 4-MePh H m.p. 135-137 C. c-17 Me t-Bu H 6-Cl O 4-ClPh H m.p. 199-201 C. c-18 Me t-Bu H 6-F SO.sub.2 H H m.p. 171-173 C. c-19 Me t-Bu H 6-CF.sub.3CH.sub.2CH.sub.2CH.sub.2O O Me Me m.p. 111-113 C. c-20 Me t-Bu Et 6-CF.sub.3CH.sub.2CH.sub.2CH.sub.2O O Me Me m.p. 75-77 C. c-21 Me t-Bu allyl 6-CF.sub.3CH.sub.2CH.sub.2CH.sub.2O O Me Me m.p. 60-62 C. c-22 Me t-Bu H 6-MeO O Me Me m.p. 90-91 C. c-23 Me t-Bu Et 6-MeO O Me Me amorphous c-24 Me t-Bu H 7-Cl O Me Me m.p. 111-113 C. c-25 Me t-Bu Et 7-Cl O Me Me m.p. 114-116 C. c-26 Me t-Bu Bn 7-Cl O Me Me viscous oil c-27 Me t-Bu H 7-BnO O Me Me m.p. 120-122 C. c-28 Me t-Bu H 6,7-(MeO).sub.2 O Me Me m.p. 134-136 C. c-29 Me t-Bu H 8-Cl O Me Me m.p. 152-153 C. c-30 Me t-Bu Et 8-Cl O Me Me m.p. 107-109 C. c-31 Me t-Bu H S Ph H m.p. 171-173 C. c-32 Me t-Bu Et O 4-FPh H nD(21.1) 1.5964 c-33 Me t-Bu Et O CH.sub.2CH.sub.2CH.sub.2CH.sub.2 nD(21.1) 1.5794 c-34 Me t-Bu Me S Ph H amorphous

[0525] Among the compounds described above, with respect to the compound in the form of an amorphous or a viscous oil, the NMR data thereof are shown below.

[0526] Compound No. (c-23): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.20 (t, 3H), 1.41 (m, 15H), 2.15 (d, 1H), 2.33 (d, 1H), 3.01 (s, 3H), 3.31 (q, 2H), 3.71 (s, 3H), 6.71 (d, 1H), 6.82 (m, 2H).

[0527] Compound No. (c-26): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.39 (m, 15H), 2.11 (d, 1H), 2.23 (d, 1H), 2.91 (s, 3H), 4.45 (q, 2H), 6.76 (d, 1H), 6.81 (d, 1H), 7.06 (d, 1H), 7.36 (m, 5H).

[0528] Compound (c-34): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.45 (s, 9H), 2.26 (m, 1H), 2.73 (m, 1H), 2.86 (s, 3H), 2.96 (s, 3H), 4.81 (m, 1H), 7.07-7.15 (m, 3H), 7.25-7.50 (m, 5H).

[0529] In addition, among the oxadiazoline compounds according to the present invention, some compounds represented by formula (II-c) are shown in Table 3, together with (melting point or characteristic).

[0530] In Table 3, Me represents a methyl group, Et represents an ethyl group, and t-Bu represents a t-butyl group.

##STR00063##

TABLE-US-00003 TABLE 3 Compound No. R.sup.1 R.sup.2 R.sup.3 (X.sup.q)m (X.sup.a)n B.sup.1 Physical property d-1 Me t-Bu Me S m.p. 210-212 C. d-2 Me t-Bu Me S m.p. 149-151 C. d-3 Me t-Bu Et S amorphous d-4 Me t-Bu H 2-Cl S m.p. 167-170 C. d-5 Me t-Bu H 2-CF.sub.3 S m.p. 151-153 C. d-6 Me t-Bu H 2,4-Et.sub.2 S amorphous d-7 Me t-Bu Et 2-Cl S m.p. 110-113 C. d-8 Me t-Bu Et 2-CF.sub.3 S m.p. 98-101 C. d-9 Me t-Bu Et 2,4-Et.sub.2 S amorphous d-10 Me t-Bu H C(Me).sub.2 m.p. 164-165 C. d-11 Me t-Bu H 4-F S m.p. 212-214 C. d-12 Me t-Bu Me 4-F S m.p. 132-135 C. d-13 Me t-Bu Et 4-F S m.p. 106-108 C.

[0531] Among the compounds described above, with respect to the compounds in the form of an amorphous, the NMR data thereof are shown below.

[0532] Compound No. (d-3): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.87 (t, 3H), 1.69 (s, 9H), 2.74 (s, 2H), 3.38 (q, 2H), 7.24-7.27 (m, 4H), 7.46-7.49 (m, 2H), 7.79-7.81 (m, 2H).

[0533] Compound No. (d-6): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.23 (t, 3H), 1.30 (t, 3H), 1.67 (s, 9H), 2.65 (q, 2H), 2.76 (s, 3H), 2.83 (q, 2H), 3.90 (s, 1H), 7.04 (s, 1H), 7.26-7.28 (m, 2H), 7.52 (m, 1H), 7.57 (m, 1H), 7.79 (m, 1H).

[0534] Compound (d-9): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.18-1.25 (m, 6H), 1.29 (t, 3H), 1.70 (s, 9H), 2.63 (q, 2H), 2.72 (s, 3H), 2.83 (q, 2H), 3.38 (q, 2H), 7.01 (s, 1H), 7.23-7.25 (m, 2H), 7.49 (m, 1H), 7.57 (s, 1H), 7.77 (m, 1H).

[0535] In addition, among the oxadiazoline compounds according to the present invention, some compounds represented by formula (I-2) are shown in Table 4, together with the physical properties (melting point or characteristic).

[0536] In Table 4, Me represents a methyl group, Et represents an ethyl group, n-Pr represents an n-propyl group, and t-Bu represents a t-butyl group.

##STR00064##

TABLE-US-00004 TABLE 4 Compound No. R.sup.1 R.sup.2 R.sup.3 (X.sup.q)m (X.sup.a)n B.sup.a Physical property e-1 Me t-Bu H 4-F CHCH m.p. 144-146 C. e-2 Me t-Bu Me 4-F CHCH m.p. 143-146 C. e-3 Me t-Bu Et 4-F CHCH m.p. 140-142 C. e-4 Me t-Bu H 4-F CH.sub.2CH.sub.2 m.p. 129-131 C. e-5 Me t-Bu Me 4-F CH.sub.2CH.sub.2 m.p. 95-97 C. e-6 Me t-Bu Et 4-F CH.sub.2CH.sub.2 amorphous e-7 Me t-Bu H CBrCH m.p. 96-98 C. e-8 Me t-Bu Me CBrCH m.p. 172-174 C. e-9 Me t-Bu Et CBrCH m.p. 70-72 C. e-10 Me t-Bu H C(Me)CH m.p. 81-83 C. e-11 Me t-Bu Me C(Me)CH m.p. 168-170 C. e-12 Me t-Bu Et C(Me)CH nD(20.7) 1.6132 e-13 Me t-Bu H C(CN)CH m.p. 170-172 C. e-14 Me C(Me).sub.2Et H CH.sub.2CH.sub.2 m.p. 110-112 C. e-15 Me C(Me).sub.2Et Me CH.sub.2CH.sub.2 m.p. 116-118 C. e-16 Me C(Me).sub.2Et Et CH.sub.2CH.sub.2 amorphous e-17 Me C(Et).sub.2H H CH.sub.2CH.sub.2 m.p. 96-98 C. e-18 Me C(Et).sub.2H Me CH.sub.2CH.sub.2 nD(21.3) 1.6012 e-19 Me C(Et).sub.2H Et CH.sub.2CH.sub.2 m.p. 94-96 C. e-20 Me C(Me).sub.2CH.sub.2(t-Bu) H CH.sub.2CH.sub.2 m.p. 120-122 C. e-21 Me C(Me).sub.2Ph H CH.sub.2CH.sub.2 m.p. 187-188 C. e-22 Et t-Bu H CH.sub.2CH.sub.2 m.p. 148-150 C. e-23 Et t-Bu Me CH.sub.2CH.sub.2 m.p. 109-111 C. e-24 Et t-Bu Et CH.sub.2CH.sub.2 m.p. 58-60 C. e-25 Et t-Bu n-Pr CH.sub.2CH.sub.2 nD(21.2) 1.6211 e-26 Me C(Et).sub.2Me H CH.sub.2CH.sub.2 m.p. 54-56 C. e-27 Me C(Et).sub.2Me Me CH.sub.2CH.sub.2 nD(21.9) 1.6139 e-28 Me C(Et).sub.2Me Et CH.sub.2CH.sub.2 nD(21.6) 1.6211 e-29 Me C(Me).sub.2Ph Me CH.sub.2CH.sub.2 m.p. 164-166 C. e-30 Me C(Me).sub.2Ph Et CH.sub.2CH.sub.2 m.p. 131-132 C. e-31 Me C(Me).sub.2Ph n-Pr CH.sub.2CH.sub.2 m.p. 110-112 C. e-32 Me C(Me).sub.2CH.sub.2(t-Bu) Me CH.sub.2CH.sub.2 amorphous e-33 Me C(Me).sub.2CH.sub.2(t-Bu) Et CH.sub.2CH.sub.2 amorphous e-34 Me C(Me).sub.2(n-Pr) H CH.sub.2CH.sub.2 m.p. 100-102 C. e-35 Me C(Me).sub.2(n-Pr) Me CH.sub.2CH.sub.2 m.p. 90-92 C. e-36 Me C(Me).sub.2(n-Pr) Et CH.sub.2CH.sub.2 nD(22) 1.5937 e-37 Me C(Me).sub.2(n-Pr) n-Pr CH.sub.2CH.sub.2 nD(22) 1.6029 e-38 Me Adamantan-1-yl H CH.sub.2CH.sub.2 m.p. 162-164 C. e-39 Me C(Me).sub.2CH.sub.2OMe H CH.sub.2CH.sub.2 m.p. 124-126 C. e-40 Me C(Me).sub.2CH.sub.2OMe Me CH.sub.2CH.sub.2 m.p. 83-85 C. e-41 Me C(Me).sub.2CH.sub.2OMe n-Pr CH.sub.2CH.sub.2 m.p. 52-54 C. e-42 Me C(Me).sub.2C(O)O(t-Bu) H CH.sub.2CH.sub.2 m.p. 132-134 C. e-43 Me C(Me).sub.2CH.sub.2OSiPh.sub.2(t-Bu) H CH.sub.2CH.sub.2 nD(22.2) 1.6311 e-44 Me C(Me).sub.2C(O)O(t-Bu) Me CH.sub.2CH.sub.2 nD(21.9) 1.5931 e-45 Me Adamantan-1-yl Me CH.sub.2CH.sub.2 m.p. 85-87 C. e-46 Me Adamantan-1-yl Et CH.sub.2CH.sub.2 nD(22) 1.5877 e-47 Me 1-Me-c-Pr H CH.sub.2CH.sub.2 m.p. 102-104 C. e-48 Me 1-Me-c-Pr Me CH.sub.2CH.sub.2 m.p. 115-117 C.

[0537] Among the compounds described above, with respect to the compounds in the form of an amorphous, the NMR data thereof are shown below.

[0538] Compound No. (e-6): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.13 (t, 3H), 1.57 (s, 9H), 2.76 (s, 3H), 3.13 (m, 2H), 3.32 (q, 2H), 3.40 (m, 1H), 3.86 (m, 1H), 6.90 (m, 1H), 7.10-7.17 (m, 4H), 7.64 (d, 1H), 7.76 (d, 1H).

[0539] Compound No. (e-16): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 0.87 (t, 3H), 1.14 (t, 3H), 1.52 (s, 6H), 2.12 (q, 2H), 2.74 (s, 3H), 3.05 (m, 2H), 3.29 (q, 2H), 3.75 (m, 2H), 7.08-7.16 (m, 6H), 7.76-7.78 (d, 2H).

[0540] Compound No. (e-32): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.05 (s, 9H), 1.62 (s, 6H), 2.20 (s, 2H), 2.71 (s, 3H), 2.89 (s, 3H), 3.08 (m, 2H), 3.72 (m, 2H), 7.08-7.12 (m, 6H), 7.82 (m, 2H).

[0541] Compound No. (e-33): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.04 (s, 9H), 1.14 (t, 3H), 1.63 (s, 6H), 2.19 (s, 2H), 2.74 (s, 3H), 3.05 (m, 2H), 3.31 (q, 2H), 3.74 (m, 2H), 7.07-7.14 (m, 6H), 7.83 (m, 2H).

[0542] In addition, Examples of other compounds are described.

Reference Example 7

Synthesis of 1-(tert-butyl)-3-(5,6,7,12-tetrahydrodibenzo[a,d][8]annulen-12-yl)thiourea

[0543] ##STR00065##

[0544] 5,6,7,12-Tetrahydrodibenzo[a,d][8]annulen-12-ol was synthesized by the method described in J. Med. Chem. 1992, 35, 2481.

[0545] 5,6,7,12-Tetrahydrodibenzo[a,d][8]annulen-12-ol (0.48 g) was dissolved in dichloromethane (7 ml). Subsequently, 1-(t-butyl)thiourea (0.32 g) and aluminum trifluoromethane sulfonate (0.10 g) were added thereto. The mixture was stirred for 2 hours, and subsequently, the reaction solvent was distilled off. The residue was purified by column chromatography with silica gel. Thereby, 0.47 g of the objective product was obtained.

[0546] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.39 (s, 9H), 2.38 (m, 2H), 2.97 (m, 2H), 3.35 (m, 2H), 5.74 (m, 1H), 6.42 (m, 1H), 6.68 (m, 1H), 7.05 (m, 4H), 7.33 (t, 2H), 7.42 (d, 2H).

Reference Example 8

Synthesis of N-tert-butyl-N-(5,6,7,12-tetrahydrodibenzo[a,d][8]annulen-12-yl)methanediimine

[0547] ##STR00066##

[0548] Triethylamine (0.58 ml) and 2-chloro-1-methylpyridinium iodide (0.54 g) were added to a solution of the thiourea (0.55 g) obtained in Reference Example 7 dissolved in acetonitrile (5 ml), and the mixture was stirred for 4 hours at room temperature. The insoluble material was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography with silica gel. Thereby, 0.45 g of the objective product was obtained.

[0549] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.29 (s, 9H), 2.32 (m, 2H), 2.97 (m, 2H), 3.25 (m, 2H), 6.38 (m, 1H), 7.05 (m, 4H), 7.13 (t, 2H), 7.63 (d, 2H).

Example 6

Synthesis of N-(tert-butyl)-2-methyl-6,7-dihydro-2H,5H-spiro[dibenzo[a,d][8]annulene-12,5-[1,2,4]oxadiazol]-3-amine (Compound No. A-1)

[0550] ##STR00067##

[0551] N-methylhydroxyamine hydrochloride (0.15 g) and trimethylamine (0.25 ml) were added to a solution of the carbodimide (0.45 g) obtained in Reference Example 8 dissolved in acetonitrile (8 ml), and the mixture was stirred for 2 hours at room temperature. The reaction solution was concentrated under reduced pressure. Subsequently, dichloromethane (8 ml) and manganese dioxide (0.13 g) were added thereto. The reaction solution was filtered using celite, and the insoluble material was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude product was washed with hexane. Thereby, 0.5 g of the objective product was obtained. The physical properties (melting point and NMR) thereof are shown below.

[0552] Melting point: 153-155 C.

[0553] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.42 (s, 9H), 2.58 (m, 4H), 2.76 (s, 3H), 2.95 (m, 2H), 3.64 (m, 1H), 7.05 (m, 4H), 7.23 (m, 2H), 7.62 (m, 2H).

Example 7

Synthesis of N-(tert-butyl)-N,2-dimethyl-6,7-dihydro-2H,5H-spiro[dibenzo [a,d][8]annulene-12,5-[1,2,4]oxadiazol]-3-amine (Compound No. A-2)

[0554] ##STR00068##

[0555] Sodium hydride (0.018 g) was added to a solution of the amine (0.1 g) obtained in Example 6 dissolved in DMF (1 ml) at 0 C., and the mixture was stirred for 30 minutes. Methyl iodide (0.04 mL) was added thereto, and the mixture was stirred for one hour at 0 C. The reaction solution was added to water with ice, and subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Subsequently, the filtrate was concentrated under reduced pressure. The obtained crude product was purified by column chromatography with silica gel. Thereby, 0.075 g of the objective product was obtained. The physical properties (melting point and NMR) are shown below.

[0556] Melting point: 111-113 C.

[0557] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm: 1.49 (s, 9H), 2.51-2.98 (m, 12H), 6.91-7.23 (m, 5H), 7.61-7.88 (m, 3H).

[0558] The oxadiazoline compounds according to the present invention (Compound No. A-3 to Compound No. A-16) produced by the same methods as those described in the Examples mentioned above are shown below together with the physical properties (refractive index or melting point).

##STR00069##

[0559] n.sub.D.sup.21.2 C.=1.6214

##STR00070##

[0560] n.sub.D.sup.21.2 C.=1.6311

##STR00071##

[0561] m.p. 165-167 C.

##STR00072##

[0562] m.p. 162-164 C.

##STR00073##

[0563] m.p. 76-78 C.

##STR00074##

[0564] n.sub.D.sup.21.2 C.=1.6398

##STR00075##

[0565] m.p. 113-115 C.

##STR00076##

[0566] m.p. 129-131 C.

##STR00077##

[0567] m.p. 138-140 C.

##STR00078##

[0568] m.p. 134-136 C.

##STR00079##

[0569] n.sub.D.sup.21.2 C.1.6097

##STR00080##

[0570] n.sub.D.sup.21.2 C.=1.613

##STR00081##

[0571] m.p. 98-100 C.

##STR00082##

[0572] n.sub.D.sup.21.2 C. 1.6097

[0573] [Biological Tests]

[0574] The following Test Examples demonstrate that the oxadiazoline compounds of the present invention (hereinafter, referred to as the compounds of the present invention) are useful as active ingredients of the formulations for controlling harmful organisms. The term part is based on weight.

[0575] (Preparation of Emulsion for Test)

[0576] 5 parts of the compound of the present invention, 93.6 parts of dimethylformamide and 1.4 parts of polyoxyethylene alkyl aryl ether were mixed and dissolved to prepare Emulsion (I) including 5% of an active ingredient. For the control, Emulsion (II) was prepared by mixing and dissolving 93.6 parts of dimethylformamide and 1.4 parts of polyoxyethylene alkyl aryl ether.

[0577] An insect mortality rate was calculated by the numerical equation shown below.

Insect mortality rate (%)={(Number of dead insects)/(Number of sample insects)}100

[0578] (Test Example 1) Efficacy Test against Mythimna separata Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Corn leaves were soaked in the diluted liquid for 30 seconds. Subsequently, the corn leaves were put on Petri dishes, followed by inoculating 5 second-instar larvae of Mythimna separata. The Petri dishes were placed in a thermostatic chamber at a temperature of 25 C. and humidity of 60%. Mortality was investigated 6 days after inoculation, and the insect mortality rate was calculated.

[0579] The efficacy test against Mythimna separata was carried out for the compounds shown in Table 13. All of the compounds shown in Table 13 demonstrated an 80% or more insect mortality rate against Mythimna separata.

TABLE-US-00005 TABLE 13 Compound Compound Compound Compound Compound Compound No. No. No. No. No. No. a-6 b-1 b-10 b-84 c-6 c-16 a-8 b-2 b-11 b-85 c-7 c-17 a-9 b-3 b-12 b-86 c-8 c-19 a-10 b-4 b-13 a-25 c-9 c-20 a-11 b-5 b-14 a-29 c-12 c-24 a-18 b-6 b-15 a-30 c-13 c-25 a-19 b-7 b-16 c-2 c-14 c-29 a-20 b-9 b-81 c-5 c-15 c-30

(Test Example 2) Efficacy Test Against Aphis gossypii

[0580] Cucumber seedlings were inoculated with nymphs of Aphis gossypii. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the cucumber plants on which the nymphs of Aphis gossypii were parasitic. The aforementioned cucumber plants were then placed in a thermostatic chamber with a temperature of 25 C. and humidity of 60%. Mortality was investigated 6 days after spraying was carried out, and the insect mortality rate of Aphis gossypii was calculated.

[0581] The efficacy test against Aphis gossypii was carried out for the compounds shown in Table 14. All of the compounds shown in Table 14 demonstrated an 80% or more insect mortality rate against Aphis gossypii.

TABLE-US-00006 TABLE 14 Compound Compound Compound Compound Compound No. No. No. No. No. a-5 b-3 a-24 c-8 A-1 a-8 b-4 a-25 c-9 A-2 a-10 b-10 a-26 c-10 A-3 a-12 b-16 c-2 c-12 a-13 b-54 c-3 c-24 a-20 b-81 c-5 c-25 a-21 b-100 c-6 c-29 b-1 b-102 c-7 c-30 b-2 b-104

(Test Example 3) Efficacy Test Against Thrips palmi (Frankliniella occidentalis)

[0582] Cucumber seedlings were inoculated with 8 adults of Thrips palmi. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the cucumber seedlings, and then air dried. The number of the parasitic larvae was counted 7 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0583] In which Nt: number of parasites at the legion spray-treated. [0584] Nc: number of parasites at the legion non-treated (control).

[0585] The efficacy test against Thrips palmi was carried out for the compounds shown in Table 15-1 and Table 15-2. All of the compounds shown in Table 15-1 and Table 15-2 demonstrated an 80% or more controlling rate against Thrips palmi.

TABLE-US-00007 TABLE 15-1 Compound No. a-1 a-2 a-3 a-4 a-5 a-6 a-8 a-9 a-10 a-11 a-12 a-13 a-14 a-15 a-16 a-17 a-22 a-23 b-1 b-2 b-3 b-4 b-5 b-6 b-7 b-8 b-9 b-10 b-11 b-12 b-13 b-14 b-15 b-16 b-17 b-21 b-22 b-24 b-29 b-30 b-31 b-32 b-33 b-34 b-35 b-39 b-45 b-46 b-47 b-48 b-49 b-50 b-51 b-52 b-53 b-55 b-56 b-57 b-59 b-61 b-63 b-68 b-69 b-70 b-72 b-73 b-74 b-75 b-78 b-79 b-80 b-81 b-82 b-83 b-84 b-85 b-86 b-92 b-93 b-94 b-95 b-96 b-97 b-98 b-99 b-100 b-101 b-102 b-103 b-104 b-105 b-106 b-107 a-25 a-31 a-35 a-36 a-37 a-38 c-5 c-12 c-24 c-31 d-1 d-2 d-3 d-4 d-5 d-6 d-7 d-8 d-9

TABLE-US-00008 TABLE 15-2 Compound No. b-108 b-127 b-147 b-165 b-182 e-1 e-26 A-1 b-109 b-128 b-148 b-166 b-183 e-2 e-27 A-2 b-110 b-129 b-149 b-167 b-184 e-3 e-28 A-3 b-111 b-130 b-151 b-168 b-185 e-4 e-29 A-4 b-112 b-135 b-152 b-170 b-187 e-5 e-32 A-5 b-113 b-136 b-153 b-171 b-191 e-6 e-33 A-6 b-117 b-137 b-154 b-172 b-192 e-11 e-34 A-7 b-118 b-138 b-155 b-173 b-193 e-14 e-35 A-8 b-119 b-139 b-156 b-174 b-194 e-15 e-37 A-9 b-120 b-140 b-157 b-175 b-196 e-16 e-38 A-10 b-121 b-141 b-159 b-176 b-197 e-20 e-39 A-11 b-122 b-142 b-160 b-177 b-198 e-21 e-41 A-12 b-123 b-143 b-161 b-178 b-199 e-22 e-42 A-13 b-124 b-144 b-162 b-179 d-11 e-23 e-43 A-14 b-125 b-145 b-163 b-180 d-12 e-24 e-47 A-16 b-126 b-146 b-164 b-181 d-13 e-25 e-48

[0586] In addition, the same test as described above was also carried out for Compound No. P1.4 described in Patent Document 1 (WO 2017/093409 A). The compound mentioned above exhibited an 80% or more controlling rate at 125 ppm. On the other hand, the compounds of Compound No. b-198 and Compound No. b-184 demonstrated an 80% or more controlling rate even at 7.8 ppm. In addition, the compound of Compound No. b-160 demonstrated an 80% or more controlling rate even at 1.9 ppm.

##STR00083##

[0587] (In the formula, R.sup.1 and R.sup.2 are Ph, R.sup.3 is t-Bu, and R.sup.4 is Me.)

(Test Example 4) Efficacy Test Against Thrips tabaci

[0588] Leaf disks of Phaseolus vulgaris were inoculated with 8 nymphs of Thrips tabaci. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the leaf disks of Phaseolus vulgaris, and then air dried. The number of the parasitic larvae was counted 7 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0589] In which Nt: number of parasites at the legion spray-treated. [0590] Nc: number of parasites at the legion non-treated (control).

[0591] The efficacy test against Thrips tabaci was carried out for the compounds shown in Table 16-1 and Table 16-2. All of the compounds shown in Table 16-1 and Table 16-2 demonstrated an 80% or more controlling rate against Thrips tabaci.

TABLE-US-00009 TABLE 16-1 Compound No. Compound No. Compound No. a-1 a-15 b-78 a-4 a-23 b-100 a-5 b-21 b-101 a-8 b-48 b-102 a-9 b-52 b-104 a-10 b-53 a-11 b-54 a-13 b-59

TABLE-US-00010 TABLE 16-2 Compound No. b-109 b-141 b-165 e-14 e-34 A-5 b-135 b-142 b-174 e-15 e-42 A-6 b-136 b-143 b-181 e-16 e-43 A-7 b-137 b-159 b-183 e-20 A-1 A-8 b-138 b-160 b-184 e-21 A-2 A-9 b-139 b-161 b-193 e-22 A-3 A-10 b-140 b-162 b-194 e-23 A-4 A-14

(Test Example 5) Drenching Test in Cucumber Seedling-Planted Pot Against Thrips palmi (Frankliniella occidentalis)

[0592] Cucumber seedlings were inoculated with 8 adults of Thrips palmi. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 500 ppm. Subsequently, 10 mL of the aforementioned diluted liquid was drenched into the cucumber seedlings, and then air dried. The number of the parasites was counted 7 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0593] In which Nt: number of parasites at the legion spray-treated. [0594] Nc: number of parasites at the legion non-treated (control).

[0595] The efficacy test against Thrips palmi was carried out for the compound of Compound No. a-10. The compound mentioned above demonstrated an 80% or more controlling rate against Thrips palmi.

(Test Example 6) Efficacy Test Against Scirtothrips dorsalis

[0596] Leaf disks of tea leaves were inoculated with 8 larvae of Scirtothrips dorsalis. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the leaf disks of tea leaves, and then air dried. The number of the parasites was counted 3 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0597] In which Nt: number of parasites at the legion spray-treated. [0598] Nc: number of parasites at the legion non-treated (control).

[0599] The efficacy test against Scirtothrips dorsalis was carried out for the compounds of Compound No. a-1 and Compound No. a-10. Both the compounds demonstrated an 80% or more controlling rate against Scirtothrips dorsalis.

(Test Example 7) Efficacy Test Against Frankliniella intonsa

[0600] Leaf disks of black-eyed pea plants were inoculated with 8 larvae of Frankliniella intonsa. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the leaf disks of black-eyed pea plants, and then air dried. The number of the parasites was counted 3 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0601] In which Nt: number of parasites at the legion spray-treated. [0602] Nc: number of parasites at the legion non-treated (control).

[0603] The efficacy test against Frankliniella intonsa was carried out for the compound of Compound No. a-10. The compound mentioned above demonstrated an 80% or more controlling rate against Frankliniella intonsa.

(Test Example 8) Penetration Test Against Thrips palmi (Frankliniella occidentalis)

[0604] Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Only the surface of the leaves of cucumber seedlings were sprayed with the diluted emulsion, and air dried. Subsequently, leaf disks thereof were prepared, and the rear face thereof was inoculated with 8 adults of Thrips palmi.

[0605] The number of the parasites was counted 2 days after inoculation. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0606] In which Nt: number of parasites at the legion spray-treated. [0607] Nc: number of parasites at the legion non-treated (control).

[0608] The penetration test against Thrips palmi was carried out for the compounds of Compound No. a-10 and Compound No. a-12. Both the compounds mentioned above demonstrated an 80% or more controlling rate against Thrips palmi.

(Test Example 9) Efficacy Test Against Thrips palmi (Frankliniella Occidentalis) Using Cotton Seedlings Planted in Pots

[0609] Cotton seedlings planted in pots for raising seedlings were inoculated with 8 adults of Thrips palmi. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the cotton seedlings mentioned above. The number of the parasitic larvae was counted 3 days after spraying. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0610] In which Nt: number of parasites at the legion spray-treated. [0611] Nc: number of parasites at the legion non-treated (control).

[0612] The efficacy test against Thrips palmi was carried out for the compound of Compound No. a-10. The compound mentioned above demonstrated an 80% or more controlling rate against Thrips palmi.

(Test Example 10) Drenching Test for Cotton Seedlings Against Thrips palmi (Frankliniella occidentalis)

[0613] Cotton seedlings planted in a cell tray were inoculated with 10 adults of Thrips palmi. Emulsion (I) was diluted with water so that the concentration of the compound of the present invention was 500 ppm. Subsequently, 7 mL of the aforementioned diluted liquid was drenched into the cotton seedlings mentioned above. The number of the parasites was counted 7 days after inoculation. The efficacy of the compounds was evaluated by the controlling rate described below.

Controlling rate (%)={1(Nt)/(Nc)}100

[0614] In which Nt: number of parasites at the legion spray-treated. [0615] Nc: number of parasites at the legion non-treated (control).

[0616] The drenching test for cotton seedlings against Thrips palmi was carried out for the compound of Compound No. a-10. The compound mentioned above demonstrated an 80% or more controlling rate against Thrips palmi.

[0617] The compounds selected at random among the oxadiazoline compounds according to the present invention exhibit the effects described above. For this reason, it can be understood that the oxadiazoline compounds of the present invention including those which cannot be demonstrated above have effects of controlling harmful organisms, and in particular, acaricidal effects, insecticidal effects and the like. In addition, it can also be understood that the oxadiazoline compounds of the present invention have effects on ectoparasites and the like which harm humans and animals.