JP2686019B2 - Termite control agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates to a novel cinnamic acid amide derivative, a method for producing the same, and a termite control agent containing the compound as an active ingredient.

[0002]

2. Description of the Related Art Damages on houses and trees caused by termites have been increasing steadily in recent years, and have become a serious economic problem. Conventionally, against such termites, toxic compounds (termiticides (termi
ticide)) or by fumigation with liquid nitrogen.

However, the use of this toxic fumigant is a serious environmental problem.

[0004]

SUMMARY OF THE INVENTION The present invention is a naturally occurring feeding inhibitory factor for termites that inhibits termite growth and viability by preventing termite feeding when the termites are contacted with the compound. It is intended to provide the resulting compound.

[0005]

[Means for Solving the Problems] As a result of intensive studies to achieve the above-mentioned objects, the present inventors have found that the anemone plant
It was found that an extract of seeds of Xylopia aethiopica and a cinnamic acid amide derivative isolated from the extract and a synthetic analog thereof have an antifeedant effect on termites,
The present invention has been completed based on the findings.

That is, a first aspect of the present invention is a compound represented by the following general formula (1):

[0007]

Embedded image Aryl-CH═CHCONHCH ₂ CH ₂ —R (1) (In the formula, Aryl is a phenyl group substituted with at least one selected from the group consisting of a hydroxyl group, a lower alkoxy group and a methylenedioxy group. And R is a phenyl group substituted with a hydroxyl group or an alkyl group having 10 to 20 carbon atoms.) Is a cinnamic acid amide derivative.

In the above formula (1), the lower alkoxy group, which is a substituent in the substituted phenyl group represented by Aryl, means an alkoxy group having 1 to 6 carbon atoms, for example, a methoxy group, an ethoxy group, a propoxy group, an isooxy group. A propoxy group may be mentioned. As the alkyl group represented by R, an alkyl group having 12 to 18 carbon atoms is particularly preferable.

Specific examples of the compound of the present invention represented by the above formula (1) include the following compounds. (1) N- [2- (4-hydroxyphenyl) ethyl]-
3-Hydroxy-4-methoxycinnamic acid amide (hereinafter referred to as "T22-5A") (2) N- [2- (4-hydroxyphenyl) ethyl]-
3,4-dihydroxycinnamic acid amide (hereinafter referred to as "T22-
6A ”. ) (3) N- [2- (4-hydroxyphenyl) ethyl]-
3,4-Methylenedioxycinnamic acid amide (hereinafter referred to as "T2
2-5AH-1 ". (4) N-octadecyl-3,4-methylenedioxycinnamic acid amide (hereinafter referred to as "T22-5AH-2") Of the compounds of the present invention, T22-5A and T22-6A.
Can be produced, for example, by extracting seeds of the anemone plant Xylopia aethiopica with a solvent and collecting the compound from the extract.

That is, the second aspect of the present invention is a plant of the Anopheles family.
Xylopia aethiopica seeds were extracted with a solvent, and from the extract, the general formula (1 ′):

[0011]

Embedded image Aryl-CH═CHCONHCH ₂ CH ₂ —R (1 ′) (In the formula, Aryl represents a 3-hydroxy-4-methoxyphenyl group or a 3,4-dihydroxyphenyl group, and R represents 4-hydroxy. A cinnamic acid amide derivative represented by a phenyl group) is collected.

The extraction solvent used in the production method of the present invention is not particularly limited, but preferred examples include methanol, acetone, chloroform and ethyl acetate. At the time of extraction, the seeds of the plant can be used as they are, but it is preferable to crush or pulverize them to enhance the contact with the solvent. It is also preferable to degrease with a hydrocarbon solvent such as hexane before extraction.

The extraction temperature is preferably within the range of room temperature to the boiling point of the solvent under normal pressure, and the extraction time varies depending on the extraction temperature and the like and may be appropriately selected. Separation and purification of the cinnamic acid amide derivative from the extract can be carried out, for example, by thin layer chromatography using silica gel or column chromatography.

The compounds of the present invention can also be chemically synthesized. That is, the third aspect of the present invention is that the general formula (2):

[0015]

Aryl-CH = CHCOX (2) (In the formula, Aryl represents a phenyl group substituted with at least one selected from the group consisting of a hydroxyl group, a lower alkoxy group and a methylenedioxy group, and X is An acid halide represented by the general formula (3):

[0016]

Embedded image NH ₂ CH ₂ CH ₂ —R (3) (wherein R is a phenyl group substituted with a hydroxyl group or the number of carbon atoms)
It represents an alkyl group of 10 to 20. ) The method for producing the cinnamic acid amide derivative is characterized by reacting with an amine represented by

In the above formula (2), examples of the halogen atom represented by X include chlorine atom and bromine atom. The acid halide (2) used as a raw material in this production method can be easily produced by halogenating the corresponding cinnamic acid derivative with thionyl chloride or the like.

The compound of the present invention and the above-mentioned extract exhibit an antifeedant effect on termites and are useful as termite control agents. That is, a fourth aspect of the present invention is a termite control agent containing the cinnamic acid amide derivative represented by the formula (1) as an active ingredient, and the fifth aspect of the present invention is a plant of the Anemoneaceae family.
It is a termite control agent containing an extract of Xylopia aethiopica seeds as an active ingredient.

The active ingredients may be used alone or in combination of two or more. These active ingredients can be used as they are, but they are usually diluted with water or a suitable organic solvent, and may be used as a water solvent or an oily agent.Moreover, emulsifiers, penetrants, stabilizers, extenders, A binder, a propellant or the like may be added to use as a dosage form such as emulsion, powder, granule, aerosol and the like.

The concentration of the active ingredient in the preparation and the application rate of the preparation are more appropriate depending on the dosage form, application method, wood treatment or soil treatment, prevention or control, type of termite, degree of damage by termites, etc. Just select it. The termite controlling agent of the present invention is extremely effective for controlling termites such as Yamato termite and house termite.

The termite-controlling agent of the present invention comprises the active ingredient itself or its formulation for the termite generation site or nest, the foundation for preventing termite damage, building members such as pillars, buildings, surrounding soil, etc. Coating, spraying, dipping, pouring,
It can be applied by spraying, mixing and the like. Further, it can be used in combination with other termite control agents depending on the condition of termite occurrence and damage. Since termite damage usually progresses simultaneously with decay by wood-rot fungi, it is particularly advantageous to use a preservative in combination. In addition, anti-humidifying agents can be used in combination.

The termite control agent of the present invention is useful for the prevention and control of termites, but it is more suitable for prevention because of its feeding suppressive action on termites. Since the active ingredient of the termite control agent of the present invention is a naturally occurring compound or an analog thereof and does not contain harmful heavy metals or halogens, there is no possibility that the termite control agent will accumulate and concentrate in the natural environment.

[0023]

The present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited to these examples. (Example 1) Preparation of extract Xylopia aet (Annonaceae) plant collected in the Ogbomosho region of the Federal Republic of Nigeria as a raw material
85 g of dried fruits of hiopica were used. The seed was taken out from the pod and crushed to obtain 16 g of a powdery product. This was degreased with 50 ml of hexane and then extracted with methanol. The residue was filtered off and the solvent was evaporated under reduced pressure to give a brown solid crude extract.

Example 2 Separation / Purification of Active Compound The compound was first separated using preparative thin layer chromatography / silica gel plate, Merck PF-254, No. 5744. Each plate was loaded with 40 mg of crude extract and developed with solvent system D (hexane: chloroform: ethyl acetate: methanol = 5: 2.5: 2.5: 1 (v / v / v / v). Rf = for the band, ie T22-5A
Each of the Rf = 0.23 bands for 0.31 and T22-6A was scraped and extracted with acetone. Acetone was distilled off under reduced pressure to obtain 5 mg of T22-5A as an amorphous powder and 20 mg of T22-6A as an amorphous white powder. To obtain the pure compound, 1 g of crude extract was applied to silica gel Merck.
It was attached to a column (20 mm x 150 mm) packed with No. 7734.
Elute with chloroform: methanol (95: 5) to give T22-
5A 24.2 mg and T22-6A 103 mg were obtained. Attempts to crystallize these compounds always give an amorphous white solid. These compounds were then analyzed and the structure confirmed by spectral analysis.

The physical properties and the like of the obtained compound are shown below. (1) N- [2- (4-hydroxyphenyl) ethyl]-
3-hydroxy-4-methoxycinnamic acid amide (T22
-5A) Property: Colorless amorphous powder Molecular weight: 313 Molecular formula: C ₁₈ H ₁₉ NO ₄ UV: λmax (nm) 318 (10082), 299 (8276), 296
(8323), 261 (5140) IR spectrum: (KBr) cm ^-1 3350, 2920, 1650, 1590, 1505, 1480, 1260, 112
0, 1040, 880, 810 (See Fig. 1) ¹ H-NMR spectrum: (270MHz, deuterated acetone, ppm
): 2.75 (2H, t, J = 7.5Hz), 3.49 (2H, m), 3.86 (3H, s),
6.52 (1H, d, J = 15Hz), 6.75 (2H, d, J = 8.5Hz), 6.83 (1H, d, J =
8Hz), 7.05 (2H, d, J = 8.5Hz), 7.02-7.14 (2H, m), 7.35 (1H,
m), 7.47 (1H, d, J = 15Hz), 8.30 (2H, bs) (see FIG. 2) ¹³ C-NMR spectrum: (67MHz, deuterated acetone, ppm)
): (OFR) 35.63 (t), 41.92 (t), 56.01 (q), 111.18
(d), 115.97 (d), 119.72 (s), 122.50 (d), 128.05 (s), 13
0.41 (d), 130.88 (s), 140.54 (d), 148.49 (s), 149.06
(s), 156.64 (d), 166.58 (s) (see FIG. 3) Mass spectrum (EI-MS): m / z: 313 (M ⁺ ), 19
3, 177, 145, 120, 107, 89, 72 Color reaction: vanillin sulfate, iodine, sulfuric acid (10
%) Solubility: Soluble in acetone and methanol. (2) N- [2- (4-hydroxyphenyl) ethyl]-
3,4-Dihydroxycinnamic acid amide (T22-6A) Properties: colorless amorphous powder Molecular weight: 299 Molecular formula: C ₁₇ H ₁₇ NO ₄ UV: λmax (nm) 322 (5273), 305 (4972), 286 (5)
280), 264 (4403) IR spectrum: (KBr) cm ^-1 3040, 2950, 1650, 1600, 1510, 1460, 1440, 135
0, 1260, 1110, 980, 820 (see FIG. 4) ¹ H-NMR spectrum: (270 MHz, heavy acetone, ppm
): 2.74 (2H, t, J = 7.5Hz), 3.46 (2H, t, J = 7.5Hz), 6.46
(1H, d, J = 15Hz), 6.79 (2H, d, J = 8.5Hz), 6.80-6.91 (4H, m),
7.06 (2H, d, J = 8.5Hz), 7.45 (1H, d, J = 15Hz) (See FIG. 5) ¹³ C-NMR spectrum: (67MHz, deuterated acetone, ppm)
): (OFR) 41.66 (t), 42.02 (t), 114.79 (d), 116.74
(d), 116.84 (s), 118.39 (s), 121.66 (d), 128.12 (s), 13
0.69 (d), 130.87 (d), 140.88 (d), 146.17 (s), 147.87
(s), 156.59 (d), 166.96 (s) (see FIG. 6) Mass spectrum (EI-MS): m / z: 299 (M ⁺ ), 28
2, 253, 226, 193, 180, 163, 137, 120, 108,91, 77 Color reaction: vanillin sulfate, sulfuric acid (10%), iodine Solubility: soluble in acetone, methanol.

Example 3 Synthesis of N- [2- (4-hydroxyphenyl) ethyl] -3,4-methylenedioxycinnamic acid amide (T22-5AH-1) 3,4-methylenedioxysilicic acid 10 g of cinnamic acid was boiled under reflux with 25 ml of thionyl chloride in 75 ml of dichloromethane. Excess thionyl chloride was removed under reduced pressure and the residue was washed with ether 10.
Dissolved in 0 ml. The ether solution was washed with 5% aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The ether was removed under reduced pressure to give the irritating acid chloride. Its structure was confirmed by ¹ H-NMR and ¹³ C-NMR spectra.

Next, 2.4 g of the acid chloride, tyramine hydrochloride
A mixture of 2 g and 5 g of sodium hydrogen carbonate was added to dimethoxyethane.
T22-5AH-1 was synthesized by heating in 80 ml under reflux for 1 hour. The solvent was evaporated, the reaction mixture was diluted with water and extracted with ether. The ether layer was washed with diluted hydrochloric acid (1M) and water, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent is a short silica gel column Merck No. 77.
Chromatography on 34, eluting with chloroform: methanol (9: 1), T22-5AH-1 1.2g
Was obtained as a colorless amorphous powder.

The physical properties of T22-5AH-1 are shown below. Melting point: 168-170 ℃ Molecular weight: 311 Molecular formula: C ₁₈ H ₁₇ NO ₄ UV: λmax (nm) 323 (15928), 300 (10050), 289
(13051), 260 (7382) IR spectrum: (KBr) cm ^-1 3850, 3520, 2950, 1660, 1610, 1540, 1510, 150
0, 1495, 1440, 1240, 1110, 1040, 980, 920, 820 (see FIG. 7) ¹ H-NMR spectrum: (270 MHz, deuterated acetone, ppm
): 2.74 (2H, t, J = 7.5Hz), 3.50 (2H, m), 6.04 (2H, s),
6.52 (1H, d, J = 16Hz), 6.75 (2H, d, J = 8.5Hz), 6.85 (1H, d, J =
7.5Hz), 7.15 (2H, d, J = 8.5Hz), 7.02-7.10 (2H, m), 7.43 (1
H, m), 7.46 (1H, d, J = 16Hz), 8.28 (1H, bs) (see FIG. 8) ¹³ C-NMR spectrum: (67MHz, heavy acetone, ppm
): (OFR) 35.64 (t), 41.91 (t), 102.38 (t), 106.82
(d), 109.12 (d), 115.99 (d), 120.90 (d), 124.23 (d), 13
0.45 (d), 130.57 (s), 130.97 (s), 139.84 (d), 149.19
(s), 149.69 (s), 156.64 (s), 166.19 (s) (see FIG. 9) Mass spectrum (EI-MS): m / z: 311 (M ⁺ ), 22
5, 191, 175, 145, 135, 120, 107, 89, 77 Color reaction: vanillin sulfate, sulfuric acid (10%), iodine Solubility: Soluble in acetone, methanol.

Example 4 N-octadecyl-3,4
-Methylenedioxycinnamic acid amide (T22-5AH-
2) Synthesis According to Example 3, 3,4-methylenedioxycinnamic acid chloride and octadecylamine were reacted in dimethoxyethane in the presence of triethylamine to produce T22-5AH.
-2 was obtained.

The physical properties of T22-5AH-2 are shown below. Property: Colorless amorphous powder Melting point: 100-101 ℃ Molecular weight: 443 Molecular formula: C ₂₈ H ₄₅ NO ₃ UV: λmax (nm) 375 (2330), 366 (2370), 319 (7)
640), 300 (5705), 289 (6922), 262 (5006) IR spectrum: (KBr) cm ^-1 3300, 2950, 2840, 1640, 1610, 1540, 1520, 150
0, 1460, 1440, 1260, 1110, 1040, 970, 920 (see FIG. 10) ¹ H-NMR spectrum: (270 MHz, CDCl ₃ , ppm
): 0.85 (3H, t, J = 6Hz), 1.19-1.38 (30H, m), 1.58 (2H,
m), 3.39 (2H, m), 5.72 (1H, m), 5.98 (2H, s), 6.14 (1H, d, J
= 15Hz), 6.77 (1H, d, J = 8.5Hz), 6.95-7.01 (2H, m), 7.58 (1
(H, d, J = 15 Hz) (see FIG. 11) ¹³ C-NMR spectrum: (67 MHz, CDCl ₃ , ppm
): (OFR) 14.09 (q), 22.66 (t), 26.96 (t), 29.33 (t),
29.67 (t), 31.89 (t), 39.80 (t), 101.37 (d), 106.29
(d), 108.48 (d), 118.87 (d), 123.74 (d), 129.31 (s), 14
0.52 (d), 148.21 (s), 148.82 (s), 166.00 (s) (see FIG. 12) Mass spectrum (EI-MS): m / z: 443 (M ⁺ ), 41
5, 308, 268, 246, 232, 218, 205, 190, 175,145, 13
5, 117, 89, 69 Color reaction: vanillin sulfate, iodine, sulfuric acid (10
%) Solubility: Soluble in acetone, chloroform, ethyl acetate and methanol.

Test Example 1 Behavior in Thin Layer Chromatography (Rf) The behavior of the above compounds in TLC was investigated in four separate solvent systems, A, B, C and D. These compounds are U
Detected by observing at 254 nm and 365 nm under a V-lamp, then sprayed with vanillin sulphate or 10% aqueous sulfuric acid. Then plate the plate at 110 ° C for 5
Heated for 10 minutes.

The solvent system used is as follows: Solvent system: A chloroform: methanol = 8.5: 1.5 (v / v) B chloroform: methanol: ethyl acetate = 8: 1: 1 (v
/ v / v) C Benzene: Acetic acid = 9: 1 (v / v) D Hexane: Chloroform: Ethyl acetate: Methanol = 5: 2.5: 2.5: 1 (v / v / v / v) Moreover, silica gel is used as the plate. Plate 60F-254 M
erck No. 5715 was used. The results are shown below.

Compound ABCD T22-5A 0.84 0.33 0.77 0.31 T22-6A 0.67 0.20 0.59 0.23 T22-5AH-1 0.94 0.47 0.90 0.41 T22-5AH-2 0.97 0.97 0.94 0.84 (Example 5) Inhibition of termite feeding As termites, the termites Reticulitermes sperat (Reticulitermes sperat) collected near Yokkaichi, Mie and Kagoshima, Kagoshima
us) (3 years old or older).

As a sample preparation, a pure compound of the present invention (purity of 99% or more) was diluted with methanol, and the following series of diluents (the following concentrations were expressed in ppm): 10000/7500/5000 / The value of 2500/1000/750/500/250/100 was used. The activity of the sample was determined by using circular filter paper (Whatman No. 1, high quality, 2.0 cm in diameter, 0.
18mm) using the choice feed bioassay (choice feed
ing bioassay). 55mm in diameter for each experiment
30 termite ants were placed in a plastic Petri dish. The bottom of the dish was covered with a layer of gelified agar (10 g / l) covered with sand (Nacalai Tesque, sand C). Each dish contains a control circular filter paper and sample treated with solvent only.
Round filter paper treated with 25 μl was placed on aluminum foil.
The same experiment was performed three times for each dose.

The amount of compound per circular filter paper is as follows: ppm: 10000 7500 5000 2500 1000 750 500 250 100 μg / filter paper: 250 187.5 125 62.5 25 18.75 12.5 6.25 2.50 μg / cm ² : 79.57 59.68 39.78 19.89 7.95 5.96 3.97 1.98 0.79 Termite, 27 ° C, 90% humidity for 14 days The filter paper was fed in the dark. Fourteen days later, the termites were removed, and the remaining filter paper was measured to evaluate the suppression of food intake.

The filter paper surface is a video interface (Hyp
erScanner adaptor A-WOK HSC-II ^R ) via APPLE MA
It measured using the video camera (HITACHI ^R Camcorder VHSC VMS72) connected to the CINTOSH SE 30 ^R computer. This method is compatible with scanning software (VIDEO M
EDIATOR ^R 1.01 Interware Co. Ltd.). The data is stored in image editing software
tware) (SUPERPAINT ^R 1.1 MS Silicon Beach Software I
nc.). Individual filter paper surface is measured by using a different software (SCALER ^R Hachinohe Firmware System). I chose square dot as the surface unit.

For each set of experiments, an intact filter paper (N =
6) was measured, and an average standard plane was calculated. Then, by referring to this surface, the percentage of the eaten area was calculated. To measure the activity of the extract, Alkofahi et al. (Alkof
ahi A., et al., 1989, ACS Symposium series No.387:
(25-43, American Chemical Society; Washington D.C.)
The feeding inhibition index described by E.

[0038]

(Equation 1) A value less than 20 indicates an antifeedant activity. A value of 0 indicates that the treated filter paper was not eaten. Values above 80 indicate a strong feeding stimulating effect.

Table 1 shows the antifeedant index (mean of three replicates (I AVG)) for all doses tested together with their standard deviation (SD).

[0040]

[Table 1]

FIGS. 13 and 14 show T22-5, respectively.
Dose response curves for A and T22-6A are shown. Compound T22-5A was more effective than T22-6A. Also, two synthetic analogs, T22-5AH-1 and T2
2-5AH-2 was also found to be significantly active at a dose of 5000 ppm.

Further, when the same test was carried out on the 1% methanol solution of the crude methanol extract obtained in Example 1, a strong effect of suppressing feeding was recognized.

[0043]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a cinnamic acid amide derivative which is a naturally-occurring compound or a synthetic analog thereof and which is highly safe and has an action of suppressing feeding on termites.

[Brief description of the drawings]

FIG. 1 is a diagram showing an IR spectrum of compound T22-5A of the present invention.

FIG. 2 is a chart showing ¹ H-NMR spectrum of a compound T22-5A of the present invention.

FIG. 3 is a chart showing ¹³ C-NMR spectrum of a compound T22-5A of the present invention.

FIG. 4 is a diagram showing an IR spectrum of compound T22-6A of the present invention.

FIG. 5 is a chart showing ¹ H-NMR spectrum of a compound T22-6A of the present invention.

FIG. 6 is a chart showing ¹³ C-NMR spectrum of a compound T22-6A of the present invention.

FIG. 7 is an IR spectrum of the compound T22-5AH-1 of the present invention.

FIG. 8 ¹ H—N of compound T22-5AH-1 of the present invention
It is a figure showing an MR spectrum.

FIG. 9: ¹³ C—N of the compound T22-5AH-1 of the present invention
It is a figure showing an MR spectrum.

FIG. 10 is a diagram showing an IR spectrum of compound T22-5AH-2 of the present invention.

FIG. 11 ¹ H-of the compound T22-5AH-2 of the present invention
It is a figure which shows a NMR spectrum.

FIG. 12: ¹³ C- of the compound T22-5AH-2 of the present invention
It is a figure which shows a NMR spectrum.

FIG. 13 shows a dose response curve for compound T22-5A of the present invention.

FIG. 14 shows a dose response curve for compound T22-6A of the present invention.

Continuation of the front page (56) Reference JP 60-190713 (JP, A) JP 60-248681 (JP, A) JP 61-10543 (JP, A) JP 61-60609 (JP , A) CHEM. PHARM. BULL. VOL. 37, NO. 4 (1989) P. 1039-1043 CHEM. PHARM. BULL. VOL. 39, NO. 7 (1991) P. 1736-1745 JOURNAL OF POLYMER R SCIENCE: POLYMER CHEMISTRY EDITION N, VOL. 21, NO. 4 (1983) P. 1111-1124

Claims (1)

(57) [Claims] 1. General formula (1): embedded image Aryl—CH═CHCONHCH ₂ CH ₂ —R (1) (wherein Aryl is selected from the group consisting of a hydroxyl group, a lower alkoxy group and a methylenedioxy group. A phenyl group substituted with at least one of the following, and R represents a phenyl group substituted with a hydroxyl group or an alkyl group having 10 to 20 carbon atoms). Control agent.