A method for adjusting radiation flux in a CT scanner, including acquiring radiation attenuation data with respect to a body being imaged by the scanner from a CT scan, in a vicinity of a first axial position along the body and determining a modulation function, depending on radial view angle, based on the data. The body is translated relative to the scanner to a second axial position along the body, and a CT scan is performed in a vicinity of the second axial position, while controlling the radiation flux impinging on the body using the modulation function.

CT scanners form images based on measurement of X-ray attenuation along multiple paths through the body of a subject. The body is generally irradiated from one side by an X-ray tube, driven by a high-voltage power supply (HVPS), as is known in the art. The X-rays are received by detectors on the opposite side of the body from the tube, which detectors generate signals proportional to the attenuated radiation flux that is incident thereon. The tube revolves around the body (along with the detectors, in third-generation scanners), so that attenuation signal data may be acquired from multiple angular "views." These data are pre-processed, filtered and back-projected to reconstruct an image of a cross-sectional slice is through the body. The body is translated axially relative to the plane of revolution of the tube, so that multiple image slices may be reconstructed, thereby producing a three-dimension CT image.
The quality of the CT image is dependent on the signal/noise ratio (SNR) of the attenuation data, which ratio generally increases with increasing radiation flux at the detectors, particularly when quantum fluctuations are the primary noise source. Therefore, the HVPS is commonly set to apply a relatively high current to the X-ray tube, resulting in a high X-ray flux irradiating the body. High flux is needed especially when imaging areas of the body in which a particularly high SNR is desired, such as the brain, or areas in which the X-ray attenuation is particularly high, such as the pelvis or shoulders, as well as in imaging the bodies of large subjects.
In other parts of the body or along different angular views through the body, however, the X-ray attenuation may not be so high, so that acceptable SNR can be attained at a relatively lower X-ray flux. In these body parts and views, the use of a higher X-ray flux than necessary is undesirable for several reasons: It exposes the subject to excessive radiation dosage, increases wear on the X-ray tube and HVPS, and adds to the cost of operating the CT scanner. Therefore, the X-ray flux should preferably be adjusted to account for the relative attenuation of the body.
Typically, the X-ray attenuation of the body increases with increasing body thickness, i.e., with increasing path length through the body. Because the cross-section of the torso is roughly elliptical, rather than circular, the path length of X-rays traversing the torso from side to side will be substantially greater than the path length from front to back. Therefore, the X-ray tube current that gives an irradiation level appropriate for views in which the tube is near the horizontal, so that the X-rays pass through the torso in the "thick" direction, will be greater than that needed for views in which the tube is near the vertical, in the "thin" direction. Operating the tube at a constant current causes either the thin views to be over-irradiated, or the thick views to be under-irradiated. Moreover, for an asymmetrical body, the noise contribution to the reconstructed image is distributed anisotropically and thus may create image artifacts.
Although the torso is thicker horizontally than vertically, it will be appreciated that other parts of the body, for example, the head, are thicker vertically than horizontally. Furthermore, X-ray attenuation along a given path depends not only on the path length through the body, but also on the types of tissues that the X-rays traverse along the path. Bone in particular attenuates X-rays much more strongly that soft tissue. Any method of compensating for thickness variations must take such differences into account.
It will also be understood that in the context of the present patent application, the terms "thickness," "thick" and "thin" used in reference to directions of radiation flux through the body refer to the combined effects of path length through the body and tissue type in determining directions of greater and lesser attenuation.
U.S. Pat. No. 5,450,462, to Toth et al., which is incorporated herein by reference, describes a CT scanner in which the current applied to the X-ray tube is varied during the revolution of the tube so as to provide greater irradiation in the thick direction than in the thin direction and generally equalize the average flux incident on the detectors in thick and thin directions. Before performing the CT scan, the X-ray path length through the subject's body as a function of view angle is estimated by performing two perpendicular, planar, longitudinal pre-scans of the body. This technique itself, however, increases the time for acquiring a CT image and adds to the radiation exposure of the subject, since ordinarily no more than one such planar pre-scan in performed, if any. It is also inexact, since it takes into account only two planar projections of the body, while the CT scan includes views from a range of angles all around the body.
U.S. Pat. No. 5,485,494, to Williams et al., which is also incorporated herein by reference, describes a technique for varying the X-ray tube current during revolution of the tube by pre-loading the HVPS with a look-up table of X-ray tube current values. This technique is applicable primarily to the pre-scanning method described in the above-mentioned '462 patent and does not overcome the shortcomings pointed out above in this regard.


An imaging system may include a multi-channel image sensor. In a multi-channel image sensor, multiple image streams from a common pixel array may be provided to a common interface transport for output on multiple logic channels. Image streams may include high-definition (HD) video and snapshot image data. Video image data may be resized using resize circuitry on the image sensors. Snapshot image data may be processed by the image sensor. Full-resolution portions of snapshot images may be output concurrently with resized HD video image data on multiple logic channels to an image signal processor. In an alternative embodiment, stack memory on the image sensor may be used to store full-resolution snapshot image data. Full-resolution snapshot image data may then be output concurrently with resized HD video image data at a slower data rate than the video image data.

This relates generally to imaging systems, and more particularly, to multi-channel imaging systems in which multiple image streams from the same pixel array share a common interface transport.
Modern electronic devices such as cellular telephones, cameras, video cameras and computers often use digital image sensors. Imagers (i.e., image sensors) may include a two-dimensional array of image sensing pixels. Each pixel receives incident photons (light) and converts the photons into electrical signals. High-speed complementary metal-oxide-semiconductor (CMOS) image pixel arrays enable high-resolution image frames to be read out at high frame rates resulting in, for example, 16 Megapixel images delivered to an image signal processor at 60 frames per second (i,e., 16 Mp60). Many image signal processors cannot process this much data in a streaming mode (e.g., video mode). This creates the need for additional image buffers that buffer an image frame before processing and may require excess amounts of power consumption by the image signal processor. Conventional image sensors may include a resizer circuit to deliver reduced resolution HD video to an image signal processor resulting in smaller amounts of data delivered to an image signal processor and lower power consumption than delivering full resolution streaming data.
Some conventional image sensors include a JPEG compressor for creating JPEG compressed snapshot images which are then combined (e.g., using a multiplexer) with the video stream on a single output channel. JPEG compression of snapshot images reduces the data rate on the output channel, however, valuable image data is lost in both a video resizing and a JPEG compressing operation.
It would therefore be desirable to provide electronic devices with improved image sensors that provide both high-resolution snapshot and resized video image data to an image signal processor.


A triazolone compound of the formula [I]:

The present invention relates to triazolone compounds, use thereof and production intermediates thereof.
WO99/07687 describes that a certain kind of triazolone compounds has a fungicidal activity.
The present invention provides compounds having a fungicidal activity, particularly an excellent fungicidal activity on fungi causing plant diseases and useful for controlling plant diseases.
Namely, the present invention provides a triazolone compound of the formula [I] (hereinafter, referred to as the compound of the invention):
wherein,
R1 represents a A1-L1-, A1-ONxe2x95x90CA2xe2x80x94, A1-ONxe2x95x90C(Me)CH2ONxe2x95x90CA2xe2x80x94, A1-C(A2)xe2x95x90Nxe2x80x94OCH2xe2x80x94, A1Sxe2x80x94C(A2)xe2x95x90Nxe2x80x94, A1-C(xe2x95x90S)NHxe2x80x94, A1Sxe2x80x94C(xe2x95x90S)NHxe2x80x94, A1Sxe2x80x94C(SA2)xe2x95x90Nxe2x80x94, A1-ONxe2x95x90C(CN)xe2x80x94, A1-ONxe2x95x90C(Me)CH2ONxe2x95x90C(CN)xe2x80x94, A1-C(CN)xe2x95x90Nxe2x80x94OCH2xe2x80x94, halogen atom, nitro or cyano;
wherein, L1 represents single bond, oxygen atom, sulfur atom, carbonyl, xe2x80x94OCH2xe2x80x94, xe2x80x94SCH2xe2x80x94, xe2x80x94C(xe2x95x90O)Oxe2x80x94, xe2x80x94OC(xe2x95x90O)xe2x80x94, xe2x80x94C(xe2x95x90O)OCH2xe2x80x94, xe2x80x94NHxe2x80x94 or C1-C6 alkylimino;
A1 and A2, which are the same or different, represent hydrogen atom, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C10 alkyl, C5-C10 cycloalkenyl, (C5-C10 cycloalkenyl) C1-C10 alkyl, phenyl, naphthyl, phenyl C1-C10 alkyl, naphtyl C1-C10 alkyl, 5- or 6-membered heterocyclic group optionally condensed with a benzene ring, or methyl substituted by 5- or 6-membered heterocyclic group optionally condensed with a benzene ring;
the alkyl, the alkenyl, the alkynyl, the cycloalkyl, the cycloalkylalkyl, the cycloalkenyl and the cycloalkenylalkyl, represented by A1 and A2, may optionally be each substituted by one or more substituents selected from the group consisting of halogen atom(s), cyano, nitro, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl)carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy and tri(C1-C10 alkyl)silyl;
the phenyl, the naphthyl, the benzene ring in the phenylalkyl, the naphthalene ring in the phenylnaphthyl, the heterocyclic group, and the heterocyclic ring in the methyl substituted by heterocylic group, represented by A1 and A2, may optionally be each substituted by one or more substituents selected from the group consisting of halogen atom(s), cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl)carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy, tri(C1-C10 alkyl)silyl, methylenedioxy and difluoromethylenedioxy;
with the proviso, when L1 is single bond, A1 is not a hydrogen atom;
T represents optionally substituted m-phenylene, optionally substituted m-azaphenylene (m-pyridinediyl) or optionally substituted m-diazaphenylene (m-diazinediyl, namely, m-pyridazinediyl, m-pyrimidinediyl or m-pyrazinediyl) bonded to R1 and to CH2 each via a carbon atom;
wherein the substituents are one or more substituents selected from the group consisting of halogen atoms, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio and (C1-C5 alkoxy)carbonyl;
and a fungicidal composition containing this compound as an active ingredient.
The present invention provides also 5-difluoromethyl-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one of the formula [L]:
a difluoroacetyl semicarbazide compound of the formula [XXVI]:
wherein R1 and T have the same meanings as described above; a semicarbazide compound of the formula [VII]:
wherein R1 and T have the same meanings as described above; 2-methyl-5-phenylbenzylamine of the formula [XVI-1]:
inorganic acid salt (for example, hydrochloric acid addition salt, hydrobromic acid addition salt, sulfuric acid addition salt) and sulfonic acid salt (for example, methanesulfonic acid addition salt) of 2-methyl-5-phenylbenzylamine; 2-methyl-5-phenylbenzyl chloride of the formula [XIII-1]:
a sulfonate compounds of the formula [XIII-2]:
wherein R9 represents a methyl or p-tolyl; N,N-dimethyl-(2-methyl-5-phenylbenzyl)amine of the formula [LI]:
inorganic acid salt (for example, hydrochloric acid addition salt, hydrobromic acid addition salt, sulfuric acid addition salt) and sulfonic acid salt (for example, methanesulfonic acid addition salt) of N,N-dimethyl-(2-methyl-5-phenylbenzyl)-amine, useful as a production intermediate for a compound of the invention.
In the present invention; as the C1-C10 alkyl represented by A1 and A2, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 1-methylpropyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 1-ethylpentyl, 3,3-dimethylbutyl, heptyl, 3,7-dimethyloctyl and the like are listed; as the C2-C10 alkenyl represented by A1 and A2, for example, vinyl, allyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl, 2-pentenyl, 3-methyl-2-butenyl and the like are listed; as the C2-C10 alkynyl represented by A1 and A2, for example, ethynyl, proparqyl, 1-methyl-2-propynyl, 2-butynyl and the like are listed; as the C3-C10 cycloalkyl represented by A1 and A2, for example, cyclopropyl, cyclopentyl, cyclohexyl and the like are listed; as the (C3-C10 cycloalkyl)alkyl represented by A1 and A2, for example, cyclopropylmethyl, cyclopentylmethyl, 2-cyclopentylethyl, cyclohexylmethyl and the like are listed; as the C5-C10 cycloalkenyl represented by A1 and A2, for example, cyclopentenyl, cyclohexenyl and the like are listed; as the (C5-C10 cycloalkenyl)alkyl represented by A1 and A2, for example, cyclopenten-1-ylmethyl, cyclohexen-1-ylmethyl and the like are listed; as the phenyl C1-C10 alkyl represented by A1 and A2, for example, phenylmethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl and the like are listed; as the naphthyl C1-C10 alkyl represented by A1 and A2, for example, xcex1-naphthylmethyl, xcex2-naphthylmethyl and the like are listed; as the 5- or 6-membered heterocyclic group optionally condensed with a benzene ring represented by A1 and A2, for example, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 3-pyridazinyl, 4-pyridazinyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isooxazolyl, 4-isooxazolyl, 5-isooxazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 1-(1,2,4-triazolyl), 3-(1,2,4-triazolyl), 4-(1,2,4-triazolyl), 2-benzothienyl, 3-benzothienyl, benzothiazol-2-yl, 2-quinolyl and the like are listed; and as the methyl substituted by a 5- or 6-membered heterocyclic group optionally condensed with a benzene ring represented by A1 and A2, for example, 2-eyridylmethyl, 4-pyridylmethyl, 2-pyrimidinylmethyl, 4-pyrimidinylmethyl, 3-pyrazolylmethyl, 2-thiazolylmethyl, 2-imidazolylmethyl, 3-(1,2,4-triazolyl)methyl, 2-quinolylmethyl and the like are listed.
Here, the alkyl, the alkenyl, the alkynyl, the cycloalkyl, the cycloalkylalkyl, the cycloalkenyl and the cycloalkenylalkyl represented by A1 and A2 may optionally be each substituted by one or more substituents selected from the group consisting of halogen atom(s) (fluorine atom, chlorine atom, bromine atom, iodine atom), cyano, nitro, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl)carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy and tri(C1-C10 alkyl)silyl; and as the alkoxy, for example, a methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy and the like are listed; as the haloalkoxy, for example, a trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy and the like are listed; as the alkylthio, for example, a methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio, hexylthio and the like are listed, as the haloalkylthio, for example, a trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio and the like are listed; as the alkylcarbonyl, for example, an acetyl, propanoyl, butanoyl, 3-methylbutanoyl andthe like are listed; as the alkoxycarbonyl, for example, a methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like are listed; as the alkylcarbonylamino, for example, an acetylamino, propanylamino, butanoylamino, 3-methylbutanoylamino and the like; and as the C3-C20 trialkylsilyl, for example, a trimethylsilyl, triethylsilyl and the like are listed.
Further, the phenyl, the naphthyl, the benzene ring in the phenylalkyl, the naphthalene ring in the phenylnaphthyl, the heterocyclic group, and the heterocyclic ring in the methyl substituted by a heterocylic group, represented by A1 and A2, may optionally be each substituted by one or more substituents selected from the group consisting of halogen atom(s) (fluorine atom, chlorine atom, bromine atom, iodine atom), cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl)carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy, tri (C1-C10 alkyl)silyl, methylenedioxy and difluoromethylenedioxy; and as the alkoxy, the haloalkoxy, the alkylthio, the haloalkylthio, the alkylcarbonyl, the alkoxycarbonyl, the alkylcarbonylamino and the trialkylsilyl, the same substituents as described above are listed; as the alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 1-methylpropyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 1-ethylpentyl, 3,3-dimethylbutyl, heptyl, 3,7-dimethyloctyl and the like are listed; as the haloalkyl, for example, trifluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl and the like are listed; and as the cycloalkyl, for example, cyclopropyl, cyclopentyl, cyclohexyl and the like are listed; and the methylenedioxy and the difluoromethylenedioxy are each substituted on adjacent two carbon atoms in a benzene ring, naphthalene ring or heterocyclic ring.
The m-phenylene, m-azaphenylene and m-diazaphenylene, bonded to R1 and to CH2 each via a carbon atom, represented by T may optionally be substituted by halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom), cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio or (C1-C5 alkoxy)carbonyl; and as the alkyl, for example, methyl, ethyl and the like are listed; as the haloalkyl, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl and the like are listed; as the alkoxy, for example, methoxy, ethoxy and the like are listed; as the haloalkoxy, for example, trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy and the like are listed; as the alkylthio, for example, methylthio, ethylthio and the like are listed; as the haloalkylthio, for example, a trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthioandthe like are listed; and as the alkoxycarbonyl, for example, methoxycarbonyl, ethoxycarbonyl and the like are listed.
As more specific examples of T, groups of the following formulae:
are listed.
Among the compounds of the invention, the compounds in which R1 is optionally substituted phenyl (namely, R1 is a A1-L1-, L1 is single bond, and A1 is optionally substituted phenyl) are preferable because of an excellent fungicidal effect. Further, the compounds in which T is m-phenylene or substituted m-phenylene are preferable because of an excellent fungicidal effect, and the preferable substituents include methyl, fluorine atom, chlorine atom and trifluoromethyl.
Particularly, the compounds of the following formula [LX] in which R1 is optionally substituted phenyl and T is methylphenylene described below are preferable because of an excellent fungicidal effect.
As the specific example of such compounds, 5-difluoromethyl-2-methyl-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one [Compound 1] of the formula:
is mentioned.
The compound of the invention can be produced according to the following Production Method A to Production Method G. Depending on the definition of R1, a desired R1 can be introduced or structured last (for example, Production Method H). In these Production Methods, a protective group can be used for protecting a functional group from reaction, if necessary.
Production Method A
The compound of the invention of the formula [I] can be produced from a formyl compound of the formula [II] by, for example, a method shown in the following chemical reaction formula:
wherein, R1 and T have the same meanings as described above.
The reaction temperature of the reaction of obtaining the compound of the invention of the formula [I] from the formyl compound of the formula [II] is usually in the range from xe2x88x9220xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 10 minutes to 10 hours. The ratio of diethylaminosulfur trifluoride used for this reaction is usually 1 to 20 mol per mol of the formyl compound of the formula [II].
The reactLion is conducted usually in a solvent, and as the solvent used, for example, halogenated hydrocarbons such as chloroform, chlorobenzene and the like, ethers such as 1,4-dioxane, tetrehydrofuran, diethyl ether and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, and mixtures thereof are listed.
The reaction solution after completion of the reaction is subjected to post treatments such as, for example, washing with a sodium bicarbonate solution before concentration of the organic layer, and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
The formyl compound of the formula [II] can be produced, for example, according to the following scheme.
wherein, R1 and T have the same meanings as described above, L2 represents a leaving group such as a chlorine atom, bromine atom, iodine atom, p-toluenesulfonyloxy, methanesulfonyloxy, trifluoromethanesulfonyloxy and the like, and R5 represents a C1-C5 alkyl (for example, methyl, ethyl and the like), phenyl or trihaloethyl (for example, trichloroethyl and the like).
A semicarbazide compound of the formula [VII] can be produced by reacting an isocyanate compound of the formula [III] with methylhydrazine. The reaction temperature of the reaction is usually in the range from xe2x88x9220xc2x0 C. to 50xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours. The ratio of methylhydrazine used for this reaction is usually 1 to 10 mol per mol of the isocyanate compound of the formula [III]. The reaction is usually conducted in a solvent, and as the solvent used, for example, ethers such as 1,4-dioxane, tetrehydrofuran, diethyl ether and the like, halogenated hydrocarbons such as chloroform, chlorobenzene and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, amides such as N,N-dimethylformamide and the like, dimethylsulfoxide and the like, and mixtures thereof are listed. The reaction solution after completion of the reaction is subjected to post treatments such as concentration, and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like. A semicarbazide compound of the formula [VIII] can be produced by reacting the isocyanate compound of the formula [III] with 1-methyl-2-hydroxyacetylhydrazine in the same manner as described above. A semicarbazide compound of the formula [IV] can also be produced by reacting the isocyanate compound of the formula [III] with hydroxyacetylhydrazine in the same manner as described above.
A compound of the formula [V] can be obtained by reacting the semicarbazide compound of the formula [IV] with a base, and for example, can be obtained by treating the compound of the formula [V] with an aqueous potassium hydroxide solution.
A compound of the formula [VI] can be obtained by reacting the semicarbazide compound of the formula [VIII] with a base, and for example, can be obtained by treating the compound of the formula [VI] with an aqueous potassium hydroxide solution.
A compound of the formula [VI] can be obtained by reacting the compound of the formula [V] with a base, and as the base used, for example, potassium carbonate is mentioned.
The compound of the formula [II] can be obtained by oxidizing the compound of the formula [VI], and as the oxidizing agent used, for example, manganese dioxide is mentioned.
The isocyanate compound of the formula [III] can be produced, for example, according to the following scheme.
wherein, R1, L2 and T have the same meanings as described above, R6 represents a C1-C4 alkyl (for example, methyl, ethyl and the like), M1 represents silver or sodium, DIBAL represents diisobutyl aluminum hydride, BuLi represents butyllithium and DMF represents N,N-dimethylformamide.
The reaction of reacting an amine compound of the formula [XVI] with triphosgene, diphosgene or phosgene to obtain the isocyanate compound of the formula [III] can be conducted, for example, by a method described in J. Org. Chem. 61, 3883-3884 (1996) or by a method described in Intermediate Production Example 3 described later.
The reaction of reducing a nitrile compound of the formula [XV] to obtain the amine compound of the formula [XVI] can be conducted, for example, by a method of reduction using aluminum lithium hydride (LiAlH4), by a method of hydrogenating the nitrile compound of the formula [XV] in the presence of a catalyst, and by the like manner; as the catalyst used in hydrogenation, for example, Raney nickel, palladium and the like are listed. Regarding the method of using Raney nickel, JP-A No. 8-291116 can be refered, and regarding the method of using pallaridum, J. Am. Chem. Soc., 50, 3370 (1928) can be refered, respectively.
The reaction of obtaining a compound of the formula [XIII] wherein L2 represents a p-toluenesulfonyloxy, methanesulfonyloxy or trifluoromethanesulfonyloxy from an alcohol compound of the formula [XII] can be conducted, for example, according to a method described in Intermediate Production Example 12 described later.
The reaction of obtaining a compound of the formula [XIII] wherein L2 represents a chlorine atom from the alcohol compound of the formula [XII] can be conducted, for example, by a method of reacting CCl4-PPh3 to the alcohol compound of the formula [XII] (specifically, method described in Intermediate Production Example 9 described later), by a method of reacting conc. Hydrochloric acid to the alcohol compound of the formula [XII] (see, Org. Synth., IV, 576 (1967)), and by the like manner. The similar methods are applicable to the compound which L2 is bromine atom or iodine atom.
The reaction of obtaining an amine compound of the formula [XVI] from a compound of the formula [XIII] can be conducted, for example, according to a method described in J. Org. Chem., 58, 270 (1993).
Other methods in the above-mentioned scheme can be conducted by ordinary methods.
An alcohol compound of the formula [XII] wherein T is the formula:
can also be produced from a benzyl chloride compound of the formula [XVII] according to the following chemical reaction formula:
wherein, R10 represents a substituent inactive in Grignard reaction among substituents defined for R1.
This reaction is conducted in a solvent, and as the solvent used, ethers such as diethyl ether, tetrahydrofuran, diglyme, triglyme and the like, and mixed solvents of these ethers with aromatic hydrocarbons such as toluene, xylene and the like. If necessary, for example, J. Am. Chem. Soc., 73, 3237 (1951) can be refered.
Among the compounds of the formula [XIII], 2-methyl-5-phenylbenzyl chloride of the formula [XIII-1] can also be produced according to the following scheme.
wherein, L2 has the same meaning as described above, and R11 represents a C1-C4 alkyl group (for example, methyl, ethyl and the like) or vinyl.
The reaction of obtaining a compound of the formula [LIII] from a compound of the formula [LII] can be conducted, for example, according to a method described in Tetrahedron, 50, 13697 (1994).
The reaction of obtaining N,N-dimethyl-(2-methyl-5-phenylbenzyl)amine of the formula [LI] from a compound of the formula [LIII] (Sommelet-Hauser rearrangement) can be conducted, for example, according to a method described in Organic Reactions, 18, 403-464 (1970). As the base used for this reaction, sodium hydride, potassium hydride, sodiumamide, potassiumamide, phenyllithium, butyllithium and the like are listed.
The reaction of obtaining 2-methyl-5-phenylbenzyl chloride of the formula [XIII-1] from N,N-dimethyl-(2-methyl-5-phenyl)benzylamine can be conducted, for example, according to a method described in Tetrahedron Lett., 24, 3233 (1983).
Production Method B
The compound of the invention of the formula [I] can be produced from a triazolone compound of the formula [XIX] according to the following chemical reaction formula.
wherein, R1, L2 and T have the same meanings as described above.
The reaction is conducted usually in the presence of a base, and as the base used, for example, inorganic bases such as sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and the like are listed.
The reaction temperature of the reaction of obtaining the compound of the invention of the formulae [I] from a triazolone compound of the formula [XIX] is usually in the range from xe2x88x9220xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
Regarding the amounts of reagents used for the reaction, the ratio of a methylating agent of the formula [IX] is 1 to 5 mol and the ratio of the base is 1 to 10 mol, per mol of the triazolone compound of the formula [XIX].
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, ethers such as 1,4-dioxane, tetrehydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, t-butyl methyl ether and the like, aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, organic bases such as pyridine, triethylamine, N-methylaniline, N,N-dimethylaniline, N,N-diethylaniline and the like, nitriles such as acetonitrile, isobutylonitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, water and the like, and mixtures thereof are listed. These solvents are selected depending on the kind of a base used.
The reaction solution after completion of the reaction is subjected to usual post treatments such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
The triazolone compound of the formula [XIX] can be produced, for example, according to the following scheme.
wherein, R1, L2 and T have the same meanings as described above, and M2 represents sodium or potassium.
An isothiocyanate compound of the formula [XXI] can be produced by reacting a compound of the formula [XIII] with a compound of the formula [XX]. A thiosemicarbazide compound of the formula [XXII] can be produced by reacting the isothiocyanate compound of the formula [XXI] with hydrazine (anhydrous hydrazine or water-containing hydrazine). A triazolinethion compound of the formula [XXIII] can be produced by reacting the thiosemicarbazide compound of the formula [XXII] with difluoroacetic acid. A sulfonic acid compound of the formula [XXIV] can be produced by oxidizing the triazolinethion compound of the formula [XXIII] using an oxidizing agent (for example, hydrogen peroxide). The triazolone compound of the formula [XIX] can be produced by hydrolyzing the sulfonic acid compound of the formula [XXIV] using an acid (for example, hydrochloric acid). In conducting processes starting from a thiosemicarbazide compound of the formula [XXII] to a triazolone compound of the formula [XIX], for example, JP-A No. 7-196630 can be referred.
The reaction solution after completion of the reaction is subjected to usual post treatments such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
Production Method C
The compound of the invention of the formula [I] can be produced from a semicarbazide compound of the formula [VII], for example, according to the following chemical reaction formula.
wherein, R1 and T have the same meanings as described above.
The reaction temperature of the above-mentioned reaction of obtaining the compound of the invention of the formula [I] from a semicarbazide compound of the formula [VII] is usually in the range from xe2x88x9220xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
Regarding the amounts of reagents used for the reaction, the ratio of a difluoroacetic anhydride is usually 1 to 5 mol per mol of the semicarbazide compound of the formula [VII].
The reaction is usually conducted in a solvent, and as the solvent used, for example, aromatic hydrocarbons such as toluene, xylene and the like, ethers such as 1,4-dioxane, tetrehydrofuran, diethyl ether and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, and mixtures thereof are listed.
In this reaction, a difluoroacetyl semicarbazide compound of the formula [XXVI] described later is formed as a by-product in some cases, however, it can be separated off by purifying the intended compound by chromatography and the like. The separated difluoroacetyl semicarbazide compound of the formula [XXVI] can be utilized as a starting material for Production Method F described later.
The reaction solution after completion of the reaction can be, for example after decomposition of excess difluoroacetic anhydride by a base such as an aqueous sodium hydroxide solution and the like, subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
Production Method D
The compound of the invention of the formula [I] can be produced from the semicarbazide compound of the formula [VII], for example, according to the following chemical reaction formula.
wherein, R1 and T have the same meanings as described above, and R7 represents a C1-C4 alkyl (for example, methyl, ethyl and the like).
The reaction temperature of the above-mentioned reaction of obtaining the compound of the invention of the formula [I] from the semicarbazide compound of the formula [VII] is usually in the range from xe2x88x9220xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
Regarding the amounts of reagents used for the reaction, the ratio of a compound of the formula [XXV] is usually 1 to 100 mol per mol of the semicarbazide compound of the formula [VII].
The reaction is conducted in the presence of a base, and as the base used, for example, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and the like, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like, alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like, and organic bases such as triethylamine, pyridine and the like are listed, and the ratio of a base is usually 0.1 to 3 mol per mol of the semicarbazide compound of the formula [VII]
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, alcohols such as methanol, ethanol and the like, ethers such as 1,4-dioxane, tetrehydrofuran, diethyl ether and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, amides such as N,N-dimethylformamide and the like, dimethylsulfoxide and the like, and mixtures thereof are listed.
In this reaction, a difluoroacetyl semicarbazide compound of the formula [XXVI] described later is formed as a by-product in some cases, however, it can be separated off by purifying the intended compound by chromatography and the like. The separated difluoroacetyl semicarbazide compound of the formula [XXVI] can be utilized as a starting material for Production Method F described later.
The reaction solution after completion of the reaction can be, after neutralization or concentration if necessary, subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
Production Method E
The compound of the invention of the formula [I] can be produced from a semicarbazide compound of the formula [VII], for example, according to the following chemical reaction formula.
wherein, R1 and T have the same meanings as described above.
The reaction temperature of the above-mentioned reaction of obtaining the compound of the invention of the formula [I] from the semicarbazide compound of the formula [VII] is usually in the range from 20xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
Regarding the amounts of reagents used for the reaction, the ratio of difluoroacetic acid is usually 1 to 100 mol per mol of the semicarbazide compound of the formula [VII].
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, aromatic hydrocarbons such as toluene, xylene and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, ethers such as 1,4-dioxane, tetrahydrofuran and the like, and mixtures thereof are listed.
In this reaction, the difluoroacetyl semicarbazide compound of the formula [XXVI] described later is formed as a by-product in some cases, however, it can be separated off by purifying the intended compound by chromatography and the like. The separated difluoroacetyl semicarbazide compound of the formula [XXVI] can be utilized as a starting material for Production Method F described later.
The reaction solution after completion of the reaction can be, after neutralization or concentration if necessary, subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
Production Method F
The compound of the invention of the formula [I] can be produced from the difluoroacetyl semicarbazide compound of the formula [XXVI], for example, according to the following chemical reaction formula.
wherein, R1 and T have the same meanings as described above.
The reaction temperature of the reaction of obtaining the compound of the invention of the formula [I] from the difluoroacetyl semicarbazide compound of the formula [XXVI] is usually in the range from 20xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 10 minutes to 10 hours.
The reaction is conducted in the presence of a base or acid, and as the base used, for example, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and the like, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like, alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like, and organic bases such as triethylamine, pyridine and the like are listed. The ratio of the base used is usually 0.1 to 10 mol per mol of a difluoroacetyl semicarbazide compound of the formula [XXVI]. As the acid used, for example, organic acids such as difluoroacetic acid, trifluoroacetic acid and the like are listed, and the ratio of the acid used is usually 1 to 100 mol per mol of the difluoroacetyl semicarbazide compound of the formula [XXVI].
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, alcohols such as methanol, ethanol and the like, ethers such as 1,4-dioxane, tetrahydrofuran, diethyl ether and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, amides such as N,N-dimethylformamide and the like, sulfoxides such as dimethyl sulfoxide and the like, water and mixtures thereof are listed. These solvents are selected and used depending on the kinds of an acid and base used.
The reaction solution after completion of the reaction can be, after neutralization or concentration if necessary, subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
The difluoroacetyl semicarbazide compound of the formula [XXVI] can also be obtained as a by-product in Production Methods C, D and E, however, can be produced, for example, according to the following scheme.
wherein, R1 and T have the same meanings as described above.
The reaction temperature in obtaining the difluoroacetyl semicarbazide compound of the formula [XXVI] from the isocyanate compound of the formula [III] is usually in the range from 0xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 10 hours.
The ratio of Nxe2x80x2-methyl-difluoroacetohydrazide used for the reaction is usually 1 to 10 mol per mol of the isocyanate compound of the formula [III].
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, alcohols such as methanol, ethanol and the like, ethers such as 1,4-dioxane, tetrahydrofuran, diethyl ether and the like, halogenated hydrocarbons such as chloroform, chlorobenzene and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, amides such as N,N-dimethylformamide and the like, dimethylsulfoxide and the like, and mixtures thereof are listed.
The reaction solution after completion of the reaction is subjected, after concentration, to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
Production Method G
The compound of the invention of the formula [I] can be produced from a compound of the formula [XIII] and a triazolone compound of the formula [L], for example, according to the following chemical reaction formula.
wherein, R1, L2 and T have the same meanings as described above.
The reaction is conducted in the presence of a base, and as the base used, inorganic bases such as lithium hydroxide, lithium hydride, sodium hydroxide, sodium hydride, potassium hydroxide, potassium hydride, sodium carbonate, potassium carbonate, and the like are listed. The reaction temperature is usually in the range from 0xc2x0 C. to 100xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
Regarding the amounts of reagents used for the reaction, the ratio of the triazolone compound of the formula [L] is usually 1 to 5 mol and the ratio of a base is usually from 1 to 10 mol per mol of the compound of the formula [XIII].
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, alcohols such as methanol, ethanol and the like, ethers such as 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and the like, aromatic hydrocarbons such as toluene, xylene and the like, organic bases such as pyridine, triethylamine, N-methylaniline, N,N-dimethylaniline, N,N-diethylaniline and the like, nitriles such as acetonitrile, isobutylonitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, water and the like, and mixtures thereof are listed. These solvents are selected depending on the kinds of a base used.
The reaction solution after completion of the reaction is subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
The triazoline compound of the formula [L] can be produced, for example, according to the following chemical reaction formula.
The reaction temperature in obtaining the triazolone compound of the formula [L] from 2-methyl semicarbazide is usually in the range from 50xc2x0 C. to 150xc2x0 C., and the reaction time is usually in the range from 1 to 100 hours.
The ratio of difluoroacetic acid used for the reaction is usually 1 to 100 mol per mol of 2-methyl semicarbazide.
The reaction is conducted in a solvent if necessary, and as the solvent used, for example, aromatic hydrocarbons such as toluene, xylene and the like, aliphatic hydrocarbons such as hexane, petroleum ether and the like, ethers such as 1,4-dioxane, tetrahydrofuranand the like, and mixtures thereof are listed.
In this reaction, 1-difluoroacetyl-2-methyl semicarbazide is formed as a by-product in some cases, however, it can be separated off by purification by chromatography and the like.
The reaction solution after completion of the reaction can be, after neutralization or concentration if necessary, subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
The triazolone compound of the formula [L] can be shown as tautomers described below.
2-methyl semicarbazide can be produced, for example, according to the following chemical reaction formula.
wherein, M3 represents sodium or potassium.
This reaction is conducted usually in an acidic aqueous solution (for example, hydrochloric acid).
Trimethylsilyl isocyanate of the above-mentioned formula in which M3 represents a trimethylsilyl is reacted with methylhydrazine, then, the reaction product is reacted with methanol. Thus, 2-methyl semicarbazide can be produced.
Production Method H
Production can be effected by the following methods (H-1) to (H-6).
(H-1): Method of producing the compound of the invention of the formula [I-2] wherein R1 in the formula [I] is phenyl, naphthyl or heterocyclic group
wherein, R8 represents phenyl, naphthyl or heterocyclic group, and the phenyl, naphthyl or heterocyclic group may optionally be each substituted by one or more substituents selected from the group consisting of halogen atoms, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl) carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy, C3-C20 Lrialkylsilyl, methylenedioxy and difluoromethylenedioxy; X and Z are the same or different and represent a chlorine atom, bromine atom, iodine atom or trifluoromethanesulfonyloxy; and T has the same meaning as described above.
(1) Method of producing aborate compound of the formula [XXVIII]
A borate compound of the formula [XXVIII] can be produced by reacting a compound of the formula [I-1] with bis(pinacolate)diboron in an organic solvent (for example, dimethyl sulfoxide, dimethylformamide) in the presence of a base (for example, potassium acetate, potassium carbonate) and a palladium catalyst (for example, dichloromethane complex of [bis(diphenylphosphino)ferrocene]dichloropalladium (II), tetrakistriphenylphosphinepalladium).
The reaction solution after completion of the reaction can be added to water, then, subjected to post treatments such as extraction with an organic solvent, concentration and the like, giving isolation of the intended compound. This intended compound can also be purified by chromatography and the like.
In this reaction, J. Org. Chem., 60, 7508-7510 (1995) can be refered, if necessary.
(2) Method of producing a compound of the invention of the formula [I-2]
The compound of the invention of the formula [I-2] can be produced by reacting the borate compound of the formula [XXVIII] with a compound of the general formula R8Z in an organic solvent (for example, dimethoxyethane) in the presence of a base (for example, potassium phosphate, potassium carbonate) and a palladium catalyst (for example, dichloromethane complex of [bis(diphenylphosphino)ferrocene]dichloropalladium (II), palladiumacetate (II), tetrakistriphenylphosphinepalladium, mixtures thereof).
A solvent in the reaction solution after completion of the reaction is distilled off, for example, then, the residue is subjected to chromatography, or the reaction solution after completion of the reaction is subjected to post treatments such as extraction with an organic solvent, concentration and the like. Thus the intended compound can be obtained. This intended compound can also be purified by re-crystallization, chromatography and the like.
In this reaction, TetrahedronLett., 38, 7645-7648 (1997) can be refered, if necessary. (H-2) Method shown in the following chemical reaction formula {method of producing the compound of the invention of the formula [I-3] wherein R1 in the formula [I] is an alkynyl having a triple bond at the bonding end}
wherein, A3xe2x80x94Cxe2x89xa1C represents a C2-C10 alkynyl optionally substituted having a triple bond at the end. This alkynyl may optionally be substituted by one or more substituents selected from the group consisting of halogen atoms, cyano, nitro, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl)carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl) carbonylamino, phenyl, phenoxy, benzyloxy and C3-C20 trialkylsilyl; and T and X are the same as described above.
The reaction of obtaining a compound of the invention of the formula [I-3] from a compound of the formula [I-1] can be conducted, for example, in an aprotic polar solvent (for example, acetonitrile, N,N-dimethylformamide) in the presence of a base (for example, secondary amine such as disopropylamine and the like, tertiary amine such as triethylamine and the like) anda catalyst (for example, combination of triphenylphosphine, copper iodide (I) and palladium catalyst such as bis(triphenylphosphine)dichloropalladium {PdCl2(PPh3)2} and the like). If necessary, WO98/03464, Example 1, Tetrahedron Lett., 16, 4467-4470 (1975), Synthesis, 1980, 627-630, or J. Org. Chem., 64, 2070-2079 (1999) can be referred.
The reaction solution after completion of the reaction can be subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, to obtain the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like. (H-3) Method shown in the following chemical reaction formula {method of producing a compound of the invention of the formula [I-2] wherein R1 in the formula [I] represents a phenyl, naphthyl or heterocyclic group}
wherein, R8, T and X are the same as described above.
The reaction of obtaining the compound of the invention of the formula [I-2] from a compound of the formula [I-1] can be conducted, for example, in a mixed solvent of water and diethoxyethane in the presence of a base (for example, inorganic base such as sodium bicarbonate) and a catalyst (for example, tetrakis(triphenyl)phosphinepalladium {Pd(PPh3)4}) (If necessary, see description in WO96/35669, Beispiel 2), or in a solvent in the presence of tetrabutylammonium bromide, base (for example, inorganic base such as potassium carbonate) and catalyst (for example, palladium acetate). The reaction solution after completion of the reaction can be subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, to obtain the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like. If necessary, J. Org. Chem., 62, 7170-7173(1997) can be referred, for example. (H-4) Method shown in the following scheme {method of producing a compound of the invention of the formula [I-5] wherein R1 in the formula [I] represents a phenoxy, naphthyloxy or heterocyclic-oxy optionally substituted}
wherein, X and T have the same meanings as described above, and A4 represents a phenyl, naphthyl or heterocyclic group, and the phenyl, naphthyl or heterocyclic group may optionally each be substituted by one or more substituents selected from the group consisting of halogen atoms, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, (C1-C9 alkyl) carbonyl, (C1-C9 alkoxy)carbonyl, (C1-C9 alkyl)carbonylamino, phenyl, phenoxy, benzyloxy, C3-C20 trialkylsilyl, methylenedioxy and difluoromethylenedioxy.
(1) Method of production from a compound of the formula [I-4]
The reaction of obtaining a compound of the invention of the formula [I-5] from a compound of the formula [I-4] can be conducted in an organic solvent (for example, methylene chloride) in the presence of a base (for example, organic base such as triethylamine and the like, inorganicbase such as sodium bicarbonate and the like) and a catalyst (for example, copper acetate (II)). If necessary, Tetrahedron Lett., 39, 2937-2940 (1998) can be refered.
(2) Method of production from a compound of the formula [I-1]
The reaction of obtaining a compound of the invention of the formula [I-5] from a compound of the formula [I-1] can be conducted in an organic solvent (for example, toluene, ethyl acetate) in the presence of a base (for example, organic base such as triethylamine and the like, inorganic base such as potassium carbonate, cesium carbonate and the like) and a catalyst (for example, copper iodide (I)). The reaction solution after completion of the reaction can be subjected to post treatment operations such as extraction with an organic solvent, concentration and the like, to obtain the intended compound. This intended compound can also be purified by re-crystallization, chromatography and the like.
In this reaction, if necessary, descriptions in J. Amer. Chem. Soc., 119, 10539-10540 (1997), J. Amer. Chem. Soc., 121, 3224-3225 (1999) and J. Amer. Chem. Soc., 121, 4369-4378 (1999) can be refered.
(3) Method of production from a compound of the formula [XXVIII]
The reaction of obtaining a compound of the invention of the formula [I-5] from a compound of the formula [XXVIII] can be conducted in an organic solvent (for example, methylene chloride) in the presence of a base (for example, organic base such as triethylamineand the like, inorganicbase such as sodium bicarbonate and the like) and a catalyst (for example, copper acetate (II)). If necessary, descriptions in Tetrahedron Lett., 39, 2937-2940 (1998) can be referred.
(H-5) Method shown in the following scheme {method of producing compounds of the inventionof the formulae [I-7] and [I-8] wherein R1 in the formula [I] represents a A1-ONxe2x95x90CA2xe2x80x94}
wherein, A5 represents a group other than a hydrogen atom among represented by A1, and L2, A2 and T have the same meanings as described above.
Compounds of the formula [I-7] in which A2 is a methyl can be produced from a compound of the formula [I-6] according to a method described in J. Org. Chem., 57, 1481-1486 (1992). Other compounds can also be produced by ordinary methods according to the above-mentioned scheme. (H-6) Method shown in the following scheme
wherein, A1, A2, L2 and T have the same meanings as described above.
Each process in the above-mentioned scheme can be conducted according to an ordinary method.
When the compound of the invention is used as an active ingredient of a fungicidal composition, it may be used itself without adding any other components, however, it is usually mixed with solid carriers, liquid carriers, surfactants and other adjuvants, to prepare emulsifiable concentrates, wettable powders, water dispersible granules, emulsion formulation, flowables, dust formulation, granules and the like, tobe used. These formulations contain the compound of the invention as an active ingredient in an amount of usually from 0.1 to 90 wt %.
The solid carrier to be used in the formulation may include, for example, the following materials in fine powder or granule form: mineral materials (e.g., kaolinite clay, attapulgite clay, bentonite clay, montmorillonite clay, acid clay, pyrophyllite, talc, diatomaceous earth, calcite), natural organic materials (e.g., stalks of corn, powder of wallnut-shell), synthetic organic materials (e.g., urea), salts (e.g., calciumcarbonate, ammonium sulfate) and synthetic inorganic materials (e.g., synthetic hydrated silicon oxide). The liquid carrier may include, for example, aromatic hydrocarbons (e.g., xylene, alkylbenzene, methylnaphthalene), alcohols (e.g., isopropyl alcohol, ethylene glycol, propylene glycol, ethylene glycol mono-ethyl ether), ketones (e.g., acetone, cyclohexanone, isophorone), vegetable oils (e.g., soybean oil, cotton seed oil), petroleum aliphatic hydrocarbons, esters, dimethyl sulufoxide, acetonitrileandwater. The surfactant may include, for example, anionic surfactants (e.g., alkylsulfate ester salts, alkyl (aryl) sulfonic acid salts, dialkylsulfosuccinic acid salts, phosphate salts of polyoxyethylenealkyl aryl ether, lignin sulfonic acid salts, naphthalenesulfonic acid formaldehyde condensations), nonionic surfactants (e.g., polyoxyethylene alkyl aryl ethers, polyoxyethylene propylene block copolymer, sorbitan fatty acid esters). The other adjuvants may include, for example, water-soluble polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone), polysaccharides (e.g., gumarabic, alginic acidand their salts, CMC (carboxy methyl cellulose), xanthan gum), inorganic materials (aluminum magnesium silicate, alumina sol), preservatives, coloringagents, PAP (isopropylacidphosphate), BHT.
The method of the application of the compound of the invention is concretely carried out, for example, by a foliar treatment, by a soil treatment, by a seed treatment and the like, also it is carried out by any method which is usually a person in the art uses.
When the compound of the invention is applied as the active ingredient of the fungicidal composition, the application amount of the active ingredient; although it may vary with a variety of plants (crops) to be protected, a variety of plant diseases to be controlled, a extent of disease damage, a formulation type, an application type, application times, weather condition and the like; is usually 1 to 5,000 g per hectare, preferably 5 to 1,000 g per hectare. In the case of emulsifiable concentrates, wettable powders, flowables and the like, they are usually applied after diluted with water, usually at a concentration of 0.0001 to 3% by weight, preferably at a concentration of 0.0005 to 1% by weight as active ingredients of the invention. In the case of dust formulations, granules and the like, they are usually applied as it is without diluting.
The compound of the invention can be used as a agricultural and horticultural antifungal agent in agricultural fields, paddy fields, orchards, tea plantations, grasslands, lawnsand the like. Increasing of the antifungal effect may be expected by using the compound of the invention with other agricultural and horticultural antifungal agent(s).
Example of the other agricultural and horticultural antifungal agents include:
azole antifungal compound such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromoconazole, epoxyconazole, difenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, myclobutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol, ipconazole, imibenconazole, imazalil, flutriafol and the like; cyclic amine antifungal compound such as fenpropimorph, tridemorph, fenpropidin and the like; benzimidazole antifungal compound such as carbendazim, benomyl, thiabendazole, thiophanate-methyl and the like; ethylen bis(dithiocarbamate) compound such as maneb, zineb, mancozeb and the like; phthalimide compound such as captan, folpet and the like; inorganic copper such as basic copper chloride, basic copper sulfate, copper sulfate, copper hydroxide and the like; organic copper such as copper-oxinate, copper-nonylphenol-sulfonate and the like; procymidone, cyprodinil, pyrimethanil, diethofencarb, thiuram, fluazinam, iprodione, vinclozolin, chlorothalonil, mepanipyrim, fenpiclonil, fludioxonil, dichlofluanid, folpet, kresoxim-methyl, azoxystrobin, trifloxystrobin, picoxystrobin, N-methyl-xcex1-methoxyimino-2-[(2,5-dimethylphenoxy)methyl]phenylacetamide, spiroxamine, quinoxyfen, fenhexamid, famoxadone, fenamidone (RP-407213), iprovalicarb, iminoctadine-triacetate, iminoctadine-albesilate, 6-iodo-3-propyl-2-propoxy-4 (3H)-quinazolinone, (Z)-N-(xcex1-cyclopropylmethoxyimino-2,3-difluoro-6-(trifluoro methyl)benzyl)-2-phenylacetamide, 2-chloro-N-(4xe2x80x2-chloro-(1,1xe2x80x2-biphenyl)-2-yl)-3-piridinecarboxamide, N-[2-(1,3-dimethylbutyl)-3-thienyl]-2,4-dimethylthiazole-5-carboxamide, N-[2-(1,3-dimethylbutyl)-3-thienyl]-3-trifluoromethyl-1-methylpyrazole-4-carboxamide and the like.
In the case of using the mixture of the compound of the invention and azole antifungal compound, the ratio of the compound of the invention to azole antifungal compound as the active ingredients is not limited to specific ratio; but when the ratio of azole antifungal compound to the compound of the invention by weight is 0.25 to 4, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and cyclic amine antifungal compound, the ratio of the compound of the invention to cyclic amine antifungal compound as the active ingredients is not limited to specific ratio; but when the ratio of cyclic amine antifungal compound to the compound of the invention by weight is 1 to 8, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and quinoxyfen, the ratio of the compound of the invention to quinoxyfen as the active ingredients is not limited to specific ratio; but when the ratio of quinoxyfen to the compound of the invention by weight is 0.25 to 2, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and spiroxamine, the ratio of the compound of the invention to spiroxamine as the active ingredients is not limited to specific ratio; but when the ratio of spiroxamine to the compound of the invention by weight is 1 to 8, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and ethylen bis (dithiocarbamate) compound, the ratio of the compound of the invention to ethylen bis(dithiocarbamate) compound as the active ingredients is not limited to specific ratio; but when the ratio of ethylen bis(dithiocarbamate) compound to the compound of the invention by weight is 1 to 20, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and phthalimide compound, the ratio of the compound of the invention to phthalimide compound as the active ingredients is not limited to specific ratio; but when the ratio of phthalimide compound to the compound of the invention by weight is 1 to 20, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and inorganic copper or organic copper, the ratio of the compound of the invention to inorganic copper or organic copper as the active ingredients is not limited to specific ratio; but when the ratio of inorganic copper or organic copper to the compound of the invention by weight is 1 to 20, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and 6-iodo-3-propyl-2-propoxy-4(3H)-quinazolinone or (Z)-N-(xcex1-cyclopropylmethoxyimino-2,3-difluoro-6-(trifluoromethyl)benzyl)-2-phenylacetamide, the ratio of the compound of the invention to 6-iodo-3-propyl-2-propoxy-4(3H)-quinazolinone or (Z)-N-(xcex1-cyclopropylmethoxyimino-2,3-difluoro-6-(trifluoromethyl)benzyl)-2-phenylacetamide as the active ingredients is not limited to specific ratio; when the ratio of 6-iodo-3-propyl-2-propoxy-4(3H)-quinazolinone or (Z)-N-((-cyclopropylmethoxyimino-2,3-difluoro-6-(trifluoromethyl)benzyl)-2-phenylacetamide to the compound of the invention by weight is 0.1 to 4, the excellent synergic effect can be achieved. In the case of using the mixture of the compound of the invention and 2-chloro-N-(4xe2x80x2-chloro-(1,1xe2x80x2-biphenyl)-2-yl)-3-piridinecarboxamide, N-[2-(1,3-dimethylbutyl)-3-thienyl]-2,4-dimethylthiazole-5-carboxamide or N-[2-(1,3-dimethylbutyl)-3-thienyl]-3-trifluoromethyl-1-methylpyrazole-4-carboxamide, the ratio of the compound of the invention to 2-chloro-N-(4xe2x80x2-chloro-(1,1xe2x80x2-biphenyl)-2-yl)-3-piridinecarboxamide, N-[2-(1,3-dimethylbutyl)-3-thienyl]-2,4-dimethylthiazole-5-carboxamide or N-[2-(1,3-dimethylbutyl)-3-thienyl]-3-trifluoromethyl-1-methylpyrazole-4-carboxamide as the active ingredients is not limited to specific ratio; but when the ratio of 2-chloro-N-(4xe2x80x2-chloro-(1,1xe2x80x2-biphenyl)-2-yl)-3-piridinecarboxamide, N-[2-(1,3-dimethylbutyl)-3-thienyl]-2,4-dimethylthiazole-5-carboxamideorN-[2-(1,3-dimethylbutyl)-3-thienyl]-3-trifluoromethyl-1-methylpyrazole-4-carboxamide to the compound of the invention by weight is 0.2 to 5, the excellent synergic effect can be achieved.
6-Iodo-3-propyl-2-propoxy-4(3H)-quinazolinone is a compound described in WO94/26722, (Z)-N-(xcex1-cyclopropylmethoxyimino-2,3-difluoro-6-(trifluoromethyl)benzyl)-2-phenylacetamide is a compound described in WO96/19442, 2-chloro-N-(4xe2x80x2-chloro-(1,1xe2x80x2-biphenyl)-2-yl)-3-piridinecarboxamide is a compound described in EP545099A, N-[2-(1,3-dimethylbutyl)-3-thienyl]-2,4-dimethylthiazole-5-carboxamide and N-[2-(1,3-dimethylbutyl)-3-thienyl]-3-trifluoromethyl-1-me thylpyrazole-4-carboxamide are compounds JP-H09-235282-A.
The compound of the invention can be applied after mixed with other agricultural and horticultural insecticidal agent(s), acaricidal agent(s), nematocidal agent(s), herbicidal agent(s), plant growth controlling agent(s) or fertilizer(s). And also the compound of the invention can be applied at the same time without mixing it beforehand.
Examples of the insecticides and acaricides include: organophosphorus compounds such as fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate], fenthion [O,O-dimethyl O-(3-methyl-4-(methythio)phenyl)phosphorothioate], diazinon [O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate], chlorpyrifos [O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate], acephate [O,S-dimethyl acetylphosphoramidothioate], methidathion [S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethylphosphorodithioate], disulfoton[O,O-diethylS-2-ethylthioethylphosphorothioate], DDVP [2,2-dichlorovinyl dimethyl phosphate], Sulprofos [O-ethyl O-4-(methylthio)phenyl S-propyl phosphorodithioate], cyanophos [O-4-cyanophenyl O,O-dimethyl phosphorothioate], dioxabenzofos [2-methoxy-4H-1,3,2-benzodioxaphosphinine-2-sulfide], dimethoate [O,O-dimethyl S-(N-methyl-carbamoylmethyl)dithiophosphate], phenthoate [ethyl 2-dimethoxyphosphinothioylthio(phenyl)acetate], malathion [diethyl (dimethoxyphosphinothioylthio))succinate], trichlorfon [dimethyl 2,2,2-trichloro-1-hydroxyethyl-phosphonate], azinphos-methyl [S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl O,O-dimethyl phosphorodithioate], monocrotophos [dimethyl (E)-1-methyl-2-(methylcarbamoyl)-vinylphosphate], ethion [O,O,Oxe2x80x2,Oxe2x80x2-tetraethyl S,Sxe2x80x2-methylenebis(phosphorodithioate)], phosphothiazate [N-(O-methyl-S-sec-butyl)phosphorylthiazolidine-2-one] and the like; carbamate compounds such as BPMC (2-sec-butylphenyl methylcarbamate), benfracarb [ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl (methyl)aminothio]-N-isopropyl-xcex2-alaninate], propoxur [2-isopropoxyphenyl N-methylcarbamate], Carbosulfan [2,3-dihydro-2,2-dimethyl-7-benzo[b]furanyl N-dibutylaminothio-N-methylcarbamate], carbaryl [1-naphthyl-N-methylcarbamate], methomyl [S-methyl-N-[(methylcarbamoyl)oxy]thioacetimidate], ethiofencarb [2-(ethylthiomethyl)phenylmethylcarbamate], aldicarb [2-methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime], oxamyl [N,N-dimethyl-2-methyl-carbamoyloxyimino-2-(methylthio)acetamide], fenothiocarb [S-4-phenoxybutyl-N,N-dimethylthiocarbamate] and the like; pyrethroid compounds such as etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl-3-phenoxybenzyl ether], fenvalerate [(RS)-xcex1-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methyl-butyrate], esfenvalerate [(S)-xcex1-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate], fenpropathrin [(RS-xcex1-cyano-3-phenoxybenzyl 2,2,3, 3-tetramethylcyclopropanecarboxylate], cypermethrin [(RS)-xcex1-cyano-3-phenoxybenzyl (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylate], permethrin [3-phenoxybenzyl (1RS)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], cyhalothrin [(RS)-xcex1-cyano-3-phenoxybenzyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate], deltamethrin [(S)-xcex1-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate], cycloprothrin [(RS)-xcex1-cyano-3-phenoxybenzyl (RS)-2,2-dichloro-1-(4-ethoxyphenyl)cyclopropanecarboxylate], fluvalinate [xcex1-cyano-3-phenoxybenzyl N-(2-chloro-xcex1, xcex1, xcex1-trifluoro-p-tolyl)-D-valinate], bifenthrin [2-methyl-biphenyl-3-ylmethyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-tri-fluoroprop-1-enyl)-2,2-dimethyl-cyclopropanecarboxylate], acrinathrin [cyano-(3-phenoxyphenyl)methyl [1R-{1xcex1(S*)-3xcex1(Z)}]-2,2-dimethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(tri-fluoromethyl)ethoxy-1-propenyl)cyclopropanecarboxylate], 2-methyl-2-(4-bromodifluoromethoxyphenyl)propyl 3-phenoxybenzyl ether, tralomethrin [(S)-xcex1-cyano-3-phenoxybenzyl (1R-cis)-3-{(1RS)(1,2,2,2-tetrabromoethyl)}-2,2-dimethyl-cyclopropanecarboxylate], silafluofen [(4-ethoxyphenyl)-{3-(4-fluoro-3-phenoxyphenyl)propyl} dimethylsilane] and the like; thiadiazine deribatives such as buprofezin [2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-triaziazinane-4-one]; nitroimidazolidine derivatives; nereistoxin derivatives such as cartap [S,Sxe2x80x2-(2-dimethylaminotrimethylene) bis(thiocarbamate)], thiocyclam [N,N-dimethyl-1,2,3-trithian-5-ylamine], bensultap [S,Sxe2x80x2-2-dimethylaminotrimethylene di (benzenethiosulfonate)] and the like;
N-cyanoamidine derivatives such as N-cyano-Nxe2x80x2-methyl-Nxe2x80x2-(6-chloro-3-pyridylmethyl)acetamidine and the like; chlorinated hydrocarbons such as endosulfan [6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine oxide], xcex3-BHC [1,2,3,4,5,6-hexachlorocyclohexane], 1,1-bis(chlorophenyl)-2,2,2-trichloroethanol and the like; benzoylphenylurea compounds such as chlorfluazuron [1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridyn-2-yloxy)phenyl)-3-(2,6-difluorobenzoyl)urea], teflubenzuron [1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea], flufenoxuron [1-(4-(2-chloro-4-trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea and the like;
formamizine derivatives such as amitraz [N,Nxe2x80x2-[(methylimino)dimethylidine]-di-2,4-xylidine], chlordimeform [Nxe2x80x2-(4-chloro-2-methylphenyl)-N,N-dimethylmethinimidamide] and the like; thiourea derivatives such as diafenthiuron [N-(2,6-diisopropyl-4-phenoxyphenyl)-Nxe2x80x2-tert-butylcarbodiimide] and the like; phenylpyrazole derivatives; tebfenozide
[N-tert-butyl-Nxe2x80x2-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide], bromopropylate [isopropyl 4,4xe2x80x2-dibromobenzylate], tetradifon [4-chlorophenyl 2,4,5-trichlorophenylsulfone], quinomethionate [S,S-6-methylquinoxaline-2,3-diyldithiocarbonate], propargate [2-(4-tert-butylphenoxy)cyclohexylprop-2-yl sulfite], fenbutatin oxide [bis[tris(2-methyl-2-phenylpropyl)tin]oxide], hexythiazox [(4RS,5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidin e-3-carboxamide], chlofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine], pyridathioben [2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazine-3(2H)-one], fenpyroximate [Lert-butyl (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]-benzoate], tebfenpyrad [N-4-tert-butylbenzyl]-4-chloro-3-ethyl-1-methyl-5-pyrazolecarboxamide], polynactin complex [tetranactin, dinactin, trinactin], milbemectin, avermectin, ivermectin, azadilactin [AZAD], pyrimidifen [5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidine-4-amine], pymetrozine [2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl)methyleneamino]-6-methyl-1,2,4-triazine] and the like.
The compound of the invention can control a variety of plant diseases, examples are described below: Blast (Pyricularia oryzae), Helminthosporium leaf spot (Cochliobolus miyabeanus) and sheath blight (Rhizoctonia solani) of rice plant; powderymildew (Erysiphegraminis), scab (Gibberella zeae), rust (Puccinia striiformis, P. graminis, P. recondita, P. hordei), snow blight (Typhula sp., Micronectriella nivalis), loose smut (Ustilago tritici, U. nuda), bunt (Tilletia caries), eyespot (Pseudocercosporella herpotrichoides), scald (Rhynchosporium secalis), leaf blight (Septoria tritici) and glume blotch (Leptosphaeria nodorum) of barley, wheat, oats and rye; melanose (Diaporthe citri), scab (Elsinoe fawcetti) and pencillium rot (Penicillium digitatum, P. italicum) of citrus; blossom blight (Sclerotinla mali), canker (Valsa mali), powdery mildew (Podosphaera leucotricha), Alternaria leaf spot (Alternaria mali) and scab (Venturia inaequalis) of apple; scab (Venturia nashicola, V. pirina), black spot (Alternaria kikuchiana) and rust (Gymnosporangium haraeanum) of pear; brown rot (Sclerotinia cinerea), scab (Cladosporium carpophilum) and Phomopsis rot (Phomopsis sp.) of peach; anthracnose (Elsinoe-ampelina), ripe rot (Glomerella cingulata), powdery mildew (Uncinula necator), rust (Phakopsora ampelopsidis), black rot (Guignardia bidwellii) and downy mildew (Plasmopara viticola) of grape; anthracnose (Gloeosporium kaki) and leaf spot (Cercospora kaki, Mycosphaerella nawae) of Japanese persimmon; anthracnose (Colletotrichum lagenarium), powdery mildew (Sphaerotheca fuliginea), gummy stem blight (Mycosphaerella melonis), stem rot (Fusarium oxysporum), downy mildew (Pseudoperonospora cubensis), late bright (Phytophthora sp.) and damping-off (Pythium sp.) of melons and cucumbers; early blight (Alternaria solani), leaf mold (Cladosporium fulvum) and late blight (Phytophthora infestans) of tomato; brown spot (Phomopsis vexans) and powdery mildew (Erysiphe cichoracearum) of eggplant; altenaria leaf spot (Alternaria japonica) and white spot (Cercosporella brassicae) of vegetables of Cruciferae; Welsh onion rust (Puccinia allii); purple stain (Cercospora kikuchii), Sphaceloma scab (Elsinoe glycines) and pod and stem blight (Diaporthe phaseolorum var. sojae) of soybean; kidney bean anthracnose (Colletotrichum lindemthianum); early leaf spot (Cercospora personata) and leaf spot (Cercospora arachidicola) of peanut; pea powdery mildew (Erysiphe pisi); early blight (Alternaria solani) and late blight (Phytophthora infestans) of potato; strawberry powdery mildew (Sphaerotheca humuli); net blister blight (Exobasidium reticulatum) and white scab (Elsinoe leucospila) of tea plant; brown spot (Alternaria longipes), powdery mildew (Erysiphe cichoracearum) anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina) and (Phytophthora nicotianae) of tobacco; beet leaf spot (Cercospora beticola); black spot (Diplocarpon rosae) and powdery mildew (Sphaerotheca pannosa) of rose; leaf spot (Septoria chrysanthemi-indici) and white rust (Puccinia horiana) of chrysanthemum; gray mold (Botrytis cinerea) and stem rot (Sclerotinia sclerotiorum) of various crops and the like.

Difluoromethyltriazolone compounds, use of the same and intermediates for the production thereof

Abstract: wherein;

Abstract: R1 represents optionally substituted phenyl or the like, T represents m-phenylene optionally substituted by methyl or the like;

Abstract: and a fungicidal composition containing it as an active ingredient.


An improved fly swatter including a working end and a handle having a terminal end which is provided with a longitudinally extending cavity in which a sound circuit board is housed. Said sound circuit board emits sound effects and/or tunes when activated by an on-off switch. In the preferred embodiment shown, said sound circuit board has a primary circuit which produces one set of sound effects and/or tunes and a secondary circuit which is activated by an inertia switch when the fly swatter strikes an object, thereby emitting a second set of sound effects and/or tunes. In one alternative embodiment illustrated, tile sound circuit board contains only one circuit which produces sound effects and/or tunes when activated by an on-off switch.

In the past the elimination of unwanted insects in the environment has been a task or duty.
This invention is of a fly swatter which contains electronics, the purpose of which is to produce amusing sounds and/or tunes while in use. This adds an element of amusement to the task of pest elimination and therefore is an improved fly swatter as is set forth mope fully hereinafter.


The present discloser is directed toward a method for detecting misalignment of a belt for a front end accessory drive system. The method includes acquiring, by a plurality of optical sensors, multiple images of the belt arranged on a series of pulleys of the drive system. The belt includes a contrast element that is detectable by the optical sensors system and is visually distinct from a color of the belt. The method further includes analyzing, by way of a controller, data indicative of the acquired images to determine whether the contrast element is present in the captured images, and identifying the belt as being misaligned in response to the contrast element being in at least one of the acquired images.

The statements in this section merely provide background information related to the present disclosure and may not constitute prior art.
A front end (i.e., engine) accessory drive (FEAD) system includes a belt (e.g., serpentine belt) that is used to drive components like alternators, water pumps, A/C compressors from a crankshaft pulley. During manufacturing of the FEAD system, the belt is typically installed manually, and visually inspected by an operator for misalignment.
Minor misalignments may be difficult to detect with the manual inspection. In particular, if the belt is misaligned such that it rubs against a case of the FEAD system or hangs over a rim of a pulley, the belt may generate noise during vehicle operation and/or begin to wear more quickly. These and other issues are addressed by the present disclosure.

Method and system for detecting misalignment of a front end accessory drive belt


A battery terminal case (16) having battery terminals is disposed at an equipment casing (12) of an electronic equipment (11) employing a battery (1) as a power supply therefor so as to be opened and closed. When the battery (1) is used, the battery terminal case (16) is opened and thus a portion (14) where the battery (1) is disposed and connected is formed on an outer portion side of the equipment casing (12). The battery (1) is connected to the battery terminals (18), (19) and thereby electrically connected to the electronic equipment (11). When the battery (1) is not used, the battery terminal case (16) is closed, thereby housing the battery terminals (18), (19) on the side of the equipment casing (12). Therefore, it is possible to employ batteries having different sizes and different capacities as long as each of them has common terminal portions.

The present invention relates to an electronic equipment employing a battery as a power supply.
An electronic equipment such as a small-sized cassette player, a disk player, a single-unit video camera-recorder, a portable telephone or the like employs a battery as a power supply therefor. A secondary battery which can be repeatedly charged, e.g., a block-shaped battery such as a nickel-cadmium battery package, a lithium battery package or the like is employed as a power supply. A large number of electronic equipments employing batteries as power supplies therefor employ an arrangement in which a battery housing portion having a battery terminal is formed in an equipment casing and a battery is housed in the battery housing portion to be electrically connected to the battery terminal. Some single-unit video camera-recorders are arranged such that a battery terminal is disposed on the side of an outer surface of an equipment casing, particularly on a rear surface side, and a battery is electrically connected to the battery terminal with being engaged and attached to the battery terminal.
Moreover, some electronic equipments are arranged such that a battery housing case is formed independently of an equipment casing and the battery housing case housing a battery is attached to the equipment body when the battery is employed as a power supply.
Since the electronic equipment employing a battery as a power supply therefor and housing the battery in a battery housing portion in its equipment casing uses a block-shaped battery, the electronic equipment has a larger battery housing portion in its equipment casing and consequently the whole casing becomes larger-sized. Additionally, a battery to be used therefor must have a predetermined shape, which prevents batteries having different capacities from being used simultaneously.
An electronic equipment having a battery terminal disposed on the outer surface side of its equipment casing encounters disadvantages that, when a battery is not used, the battery terminal is exposed to the outside, which aggravates an appearance of the electronic equipment and may damage the battery terminal. Moreover, an electronic equipment having a battery housing case formed independently of its equipment casing and attached to the equipment casing when a battery is used, encounters disadvantages that the whole equipment becomes large-sized upon use of the battery, which leads to inconvenience in carrying the electronic equipment and particularly in portability. Also, in this case, a battery to be used therefor must have a predetermined shape, which prevents batteries having different capacities from being used simultaneously.

Electronic equipment with removable battery terminal


A method initializes a federated computer system from a fabric of nodes connected by a federated interface. Each node casts a vote to the federated interface for a candidate firmware version supported by the node casting the vote. The candidate firmware version having received the greatest number of votes is identified, and the computer system is initialized as a federated system of the nodes that support the firmware version identified as having received the greatest number of votes. A process of iterative voting may be used to identify a greater number of nodes supporting a compatible firmware version.

1. Field of the Invention
The present disclosure relates to federated computer systems and methods for initializing a federated computer system.
2. Background of the Related Art
A data center is a facility where computer equipment and related infrastructure are consolidated for centralized operation and management. Computer equipment may be interconnected in a datacenter to produce large, powerful computer systems that are capable of storing and processing large amounts of data for entities such as large corporations, web hosting services, and Internet search engines. A data center may house any number of racks, each capable of holding a large number of servers and supporting equipment, such as switches, power supplies, network communications interfaces, environmental controls, and security devices. Servers and supporting equipment are typically housed in rack-mounted, multi-server enclosures (e.g. a multi-blade chassis) and arranged in a high-density configuration. This type of arrangement uses space efficiently while providing physical access to the equipment and enabling the circulation of cool air. As many servers and rack-mounted enclosures as needed may be interconnected to produce a system having the desired performance.
A federated computer system involves multiple nodes interconnected to form a larger computer system. A federated computer system also requires the use of multiple firmware images, with one set of firmware per node. The multiple sets of firmware are responsible for coordinating an initial sequencing of the federated system. In order to properly coordinate this sequencing, the sets of firmware must be compatible or match. Firmware for each server or node in a federated computer system may be periodically flash updated. When a node fails to be updated with its peers, such as through user error or a firmware update process failure, the system may no longer be able to initialize in the federated configuration. The conventional response to such a failure is either to simply stop the initialization and emit an error from all nodes or to initialize each node as an independent system in a non-federated configuration.

Forming a federated system with nodes having greatest number of compatible firmware version

Lenovo Enterprise Solutions (Singapore) Pte. Ltd.


A system and method of providing and validating a bar-code on a lottery ticket to allow secure verification of tickets is described. Lottery ticket information comprising unique identifying information uniquely identifying the lottery ticket and validation information for use in determining a prize value associated with the lottery ticket is generated. First redundancy information is generated using the validation information and a portion of the unique identifying information. The first redundancy information used for checking the integrity of subsequently received validation information. The validation information is encrypted and second redundancy information is generated using the unique identifying information and the encrypted validation information. A first bar-code is constructed using the unique identifying information, the encrypted validation information and the second redundancy information. The first bar-code is printed on the lottery ticket and at least a part of the first bar-code is covered with scratch-off material.

Lottery tickets can be generally divided into instant and on-line lottery tickets. For instant lottery tickets, winning tickets are predetermined, whereas for on-line lottery tickets, winning tickets are unknown until an event, such as a number draw, takes place. The significance of this difference is that for instant lottery tickets, information about the prize is available at the time of printing and the printed ticket includes information that can be connected or related to the prize information. Thus, it is important for the instant lottery ticket and its associated prize information to be secure in order to maintain the integrity of the lottery system.
The security or integrity of a lottery system may be attacked in numerous ways. For example, an external fraudster may attempt to determine and submit winning ticket numbers by repeatedly submitting ticket information that is used to determine and allocate winnings. Such an attack may be referred to as a fishing type of attack as the fraudster is fishing for a valid winning ticket information. This type of attack may be successful if the fraudster guesses a valid winning ticket information. The system is tricked into paying the fraudster for the winning prize, assuming the prize is below a given threshold above which the prize must be redeemed in person; however the fraudster may not have purchased the ticket and has merely guessed the correct ticket information.
An internal fraudster, such as someone having access to internal lottery administration systems, may attempt to determine the location a winning ticket was sent to. The internal fraudster may then attempt to purchase tickets from the determined location, thus increasing the probability of winning. Typically, an internal fraudster will attempt to locate a winning ticket having a large prize in order to make the possibility of purchasing a large amount of tickets worthwhile.
Additionally, the security or integrity of the lottery system may be attacked through the collusion of external and internal fraudsters. Regardless of who is involved in attempting to defraud the lottery system, there are various ways of attacking the lottery system.
Previous attempts at improving the security or integrity of the lottery system have generally focused on preventing external fraudsters from pre-screening tickets for winning tickets or otherwise tampering or defrauding the lottery system.
Traditionally, instant lottery tickets were validated by scanning a validation bar-code at a ticket terminal and the terminal operator manually keyed-in a security code. Because the security code was hidden under a scratch-off material, the player and the lottery administration were given assurance that the vendor did not pre-screen the lottery ticket to pick out the winning tickets. However, the security code was not fool-proof as vendors attempted to guess the security code, which may be a 3 or 4 digit number. Moreover, human errors also contributed to errors in the validation process.
Thus, there have been attempts to further streamline the validation process by eliminating the security code and incorporating all the validation information into the bar-code. This allowed the instant lottery ticket to be verified simply by scanning the validation bar-code without manual human input. Security of such bar-codes may be increased by encrypting the bar-code contents.
However, a shortcoming of this solution was that the bar-code contained information a fraudster could use to obtain the prize information. The combination of the lottery ticket information and the security code could jeopardize the integrity of the lottery system.
Therefore, a method of bar-coding lottery information on an instant lottery ticket that increases or ensures the integrity of the lottery system would be desirable.

Barcoded lottery ticket, system and method for producing and validating the same


A reel for the management, transport, and storage of flexible materials such as electrical cords, air hoses, and the like, comprises a hollow cylindrical central hub with a pair of disk-like side plates radially attached to the outer ends of the hub, a slidable hand grip mounted on said reel and a rotatable winding knob for controllable rotation of the reel by an operator. The cord take-up portion of the hub has a provisional retainer shaped to receive a loop formed, preferably, in the middle of the cord's length. Once the loop is hooked over the provisional retainer, an operator reels in both halves of the cord simultaneously by turning with the winding knob. Conversely, holding the reel by the slidable hand grip with one hand and pulling outward on both ends of the cord simultaneously with the free hand, unreels the cord as needed. Once the cord is fully unwound from the hub, the provisional retainer allows it to falls free of the reel for unfettered use.

The prior art is replete with novel means to manage electrical cords and other lengthy flexible materials such as hoses and cables. Except for necessarily complex systems for industrial applications, such as the structure taught in U.S. Pat. No. 3,840,713, issued to Carpentier, a vast number of these devices are overly elaborate structures which, on their faces, appear to be clever and effective solutions to the age-old problem of cord management. Exemplary of the prior art of this category are U.S. Pat. Nos. 2,952,420 issued to Von Hoorn; U.S. Pat. No. 4,390,142 issued to Cheng; and, U.S. Pat. No. 5,992,787, issued to Burke; and, U.S. Pat. No. 7,984,798 B1, issued to Hall.
Unfortunately, these devices require many stages and operations in their manufacture, resulting in great expense for the manufacturer in materials, tooling, and labor, the added costs of which are passed on to the consumer in the form of higher prices. In addition, these devices sacrifice simplicity of structure and operation to produce their questionable advantages. For instance, it is a characteristic of this class of cord managing devices to fold, or bend, the cord sharply in order to make it comply with the requirements of the device. In the case of cords that carry electrical current, this is extremely bad practice and can lead to overheating, failure of the cord, and, in worst-case scenarios, fire and electrocution. However, operationally, there is another major disadvantage in these devices: the electrical cord is captured within them and must remain encumbered by the device at all times. Only in the extreme situation would it be advantageous for the operator to fully remove the cord from the device for unrestricted use.
Another disadvantage of devices of this class of prior art is complete disengagement of the cord from the device requires the performance of a number of annoying, and time consuming, manipulations.
There are, however, other prior art devices that are more elegant in their simplicity and more straightforward in their functionality. Devices of this class of cord management tools are typified by their low costs of manufacture and general ease of use. Examples include U.S. Pat. No. Des. 314,910, issued to VanSkiver; U.S. Pat. No. Des. 359,440, issued to Stewart; and, U.S. Pat. No. Des. 408,720, issued to Sheng. Each of the first two patents features two means for fastening an end of an electrical cord to the device for winding upon a hub: a hook to capture an end of the cord, located within the cord winding area next to the hub and one, or more, keyhole-shaped receptacles let into a side plate of the device for retaining a cord end. These devices exemplify simplicity and general usefulness and are the basis upon which the present invention is an improvement. However, these prior art devices also have disadvantages which will be discussed later in this specification.

Reel for improved handling of lengthy flexible materials such as electrical cords, and the like


A fatigue degree determination device includes a fatigue degree determination unit. A first biological heart rate is acquired while a user is awake and at rest, based on a biological heart rate measured from the user. A second biological heart rate is acquired while the user is sleeping, based on the biological heart rate measured from the user. The fatigue degree determination unit determines a fatigue degree of the user, based on information read out from a storage medium, the first biological heart rate and the second biological heart rate. The storage medium stores the information in which a degree of change of one biological heart rate relative to the other biological heart rate of a biological heart rate while a person is awake and at rest and a biological heart rate while the person is sleeping and a fatigue degree are associated with each other.

A device or system configured to provide information about user's health and the like on the basis of biological information measured from a user has been known (refer to Patent Documents 1 to 3).
Patent Document 1 discloses a system configured to evaluate user's chronic fatigue on the basis of a user's heartbeat interval. The system is configured to perform frequency analysis of the heartbeat interval while the user is sleeping, and to determine whether or not the chronic fatigue on the basis of a result of the frequency analysis.
Patent Document 2 discloses a wearable device configured to obtain stress information of a user on the basis of a heart rate of the user who is in a deep sleep state.
Patent Document 3 discloses a device that, when a user's biological heart rate measured at any timing is lowered by a threshold value or greater with respect to biological heart rate data while the user is awake, which is stored in advance, determines that the user is fatigued, asleep or fatigued and asleep, and when a difference between the user's biological heart rate measured at any timing and biological heart rate data while the user is sleeping, which is stored in advance, is smaller than a threshold value, determines that the user is fatigued, asleep or fatigued and asleep.
Patent Document 1: JP-A-2015-109888
Patent Document 2: JP-A-2015-173684
Patent Document 3: JP-A-2015-195982

Fatigue degree determination device, and fatigue degree determination method