Triticonazole | 131983-72-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Triticonazole
• 英文别名: 2-(4-chlorobenzylidene)-5,5-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol；Triticonazole [ISO]；(5Z)-5-[(4-chlorophenyl)methylidene]-2,2-dimethyl-1-(1,2,4-triazol-1-ylmethyl)cyclopentan-1-ol
• CAS: 131983-72-7
• 化学式: C₁₇H₂₀ClN₃O
• 分子量: 317.818
• InChiKey: PPDBOQMNKNNODG-ZROIWOOFSA-N

物化性质

• 熔点：
  143～149℃
• 沸点：
  498.7±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：30 mg/ml； DMSO：30 mg/ml；乙醇：30 mg/ml；乙醇:PBS(pH 7.2) (1:1): 0.5 mg/ml
• 颜色/状态：
  White powder
• 气味：
  Odorless at 22 °C
• 蒸汽压力：
  3.4X10-9 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Slight decomposition at 180 °C.

• 分解：
  When heated to decomposition it emits toxic vapors of /nitrogen oxides and Cl-/.

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者身体前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/遗传毒性/ 人类淋巴细胞（全血）在第一次试验（男性）中用Triticonazole（RPA 400727，纯度：90.9%）以7.751至800微克/毫升的浓度处理，在第二次试验（女性）中以33.79至800微克/毫升的浓度处理，在激活和非激活条件下于37摄氏度下进行。在激活条件下，细胞暴露于试验材料3小时，洗涤后额外孵化17小时（第一次试验）和17或41小时（第二次试验）。在非激活实验中，细胞暴露于试验材料20小时（第一次试验）和20或44小时（第二次试验）。使用预先用Aroclor 1254处理过的雄性大鼠的肝脏匀浆S9组分来代谢试验材料。在第一次试验中，在非激活条件下，在两个较高处理水平上，细胞畸变数量呈剂量相关增加（p<0.01和p<0.001）。大多数畸变是染色体或染色单体缺失。这种细胞畸变数量的增加在第二次试验中细胞孵化20小时时不那么明显。在未激活且暴露于试验材料44小时的一个处理水平上，细胞畸变数量增加（p<0.05）。试验材料的代谢似乎没有导致染色体畸变细胞数量的增加。试验结果提示在没有激活的情况下有阳性反应。结果表明，试验材料可能具有遗传毒性。表明的副作用：在没有激活的情况下，染色体畸变细胞的数量增加。阳性对照在激活和非激活条件下都是有效的。

/GENOTOXICITY/ Human lymphocytes (whole blood) were treated with Triticonazole (RPA 400727, purity: 90.9%) at concentrations ranging from 7.751 to 800 ug/mL in the 1st trial (male) and 33.79 to 800 ug/mL in the 2nd trial (female) under conditions of activation and non-activation at 37deg C. Under conditions of activation, the cells were exposed to the test material for 3 hrs, washed and then incubated for an additional 17 hrs (1st trial) and 17 or 41 hrs (2nd trial). In the non-activated assays, the cells were exposed to the test material for 20 hrs (1st trial) and 20 or 44 hrs (2nd trial). A liver homogenate S9 fraction from male rats pretreated with Aroclor 1254 was used to metabolize the test material. In the first trial, an increase in cells with aberrations was noted in a dose-related manner at the two higher treatment levels evaluated (p<0.01 and p<0.001) under conditions of non-activation. The majority of the aberrations were chromosomal or chromatid deletions. This increase in the number of cells with aberrations was not as evident in the 2nd trial for the cells incubated for 20 hrs. For the one treatment level evaluated after exposure to the test material for 44 hrs without activation, the number of cells with aberrations was increased (p<0.05). Metabolism of the test material did not apparently result in an increased number of cells with chromosomal aberrations. The results of the assay were suggestive of a positive response without activation. The results indicate that the test material is possibly genotoxic. Indicated adverse effect: increased numbers of cells with chromosomal aberrations without activation. The positive controls were functional for both activation and non-activation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/迟发型接触超敏反应是通过使用30只年轻的成年雄性和雌性Dunkin Hartley白化豚鼠，通过Magnusson-Kligman最大化测试来评估的。十只雄性和十只雌性豚鼠在第一天接受了以下三种治疗的皮内注射：Freunds完全佐剂；5% w/v曲康唑（纯度：92.5%）活性成分产品在丙二醇中；以及5% w/v曲康唑（纯度：92.5%）在佐剂中。七天后，同一部位的皮肤通过局部应用50% w/v曲康唑在丙二醇中处理，并在48小时内用封闭敷料覆盖测试部位。同一诱导程序同时对一组十只雄性和十只雌性动物进行了对照，除了所有剂量的测试材料被替换为载体（丙二醇）。在第22天，所有动物通过在左腹部封闭应用丙二醇，以及在右侧两个部位应用50% w/v曲康唑在丙二醇中和10% w/v曲康唑在丙二醇中进行挑战。封闭敷料在第二天被移除，测试部位在大约24小时和48小时后进行评分。重复给予曲康唑没有在豚鼠中引起迟发型接触超敏反应。根据这项研究的结果，建议对曲康唑进行非致敏分类。皮内注射5% w/v曲康唑在丙二醇或佐剂中引起了轻微或中度的红斑、苍白和变色。局部应用50% w/v曲康唑在丙二醇中在大多数动物中引起了几乎无法察觉或轻微的红斑和脱屑。没有观察到对10% w/v曲康唑在丙二醇中的挑战的显著反应。在用50% w/v曲康唑在丙二醇中进行挑战后，三只对照动物和没有测试动物出现了显著反应（轻微红斑）。实验室认为对照动物的反应是偶然的。

/LABORATORY ANIMALS: Acute Exposure/ Delayed contact hypersensitivity was assessed using 30 young adult male and female Dunkin Hartley albino guinea pigs by the Magnusson-Kligman Maximization Test. Ten males and ten females received intradermal injections of each of the following three treatments: Freunds Complete Adjuvant; 5% w/v Triticonazole (purity: 92.5%) active ingredient product in propylene glycol; and 5% w/v Triticonazole (purity: 92.5%) in the adjuvant on Day 1. Seven days later the same area of skin was treated by topical application of 50% w/v Triticonazole in propylene glycol and the test site was covered by an occlusive dressing for 48 hours. The same induction procedures were carried out on a concurrent control group of ten male and ten female animals, except the test material was replaced by vehicle (propylene glycol) in all doses. On Day 22, all animals were challenged by occluded application of propylene glycol to the left flank and 50% w/v Triticonazole in propylene glycol and 10% w/v Triticonazole in propylene glycol to two sites on the fright flank. The occlusive dressings were removed on the following day and the test sites were scored approximately 24 and 48 hours later. Repeated administrations of Triticonazole did not cause delayed contact hypersensitivity in guinea-pigs. A non-sensitizer classification is proposed for Triticonazole based on the results of this study. Intradermal injection of 5% w/v Triticonazole in propylene glycol or the adjuvant caused slight or moderate erythema, pallor and discoloration. Topical application of 50% w/v Triticonazole in propylene glycol caused barely perceptible or slight erythema and exfoliation in most animals. No significant response was observed to challenge with 10% w/v Triticonazole in propylene glycol. A significant response (slight erythema) was observed in three control and no test animals following challenge with 50% w/v Triticonazole in propylene glycol. The laboratory considered that the reaction with the control animal was incidental.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  N
• 危险类别码：
  R51/53
• 危险品运输编号：
  UN 3077
• WGK Germany：
  2
• RTECS号：
  GY4705000
• 海关编码：
  2933990016
• 安全说明：
  S61

制备方法与用途

农用杀菌剂灭菌唑

灭菌唑是由Rhone-Poulenc农用化学品公司研制的新型广谱内吸性三唑类农用杀菌剂，为甾醇生物合成中C-14α-脱甲基化酶抑制剂。它主要用于防治禾谷类、豆科作物和果树病害，对白粉病、菌核病、枯萎病、纹枯病、网枯病、锈病、叶斑病和云纹病等作物病害均具有良好的防治效果。灭菌唑作为种衣剂能防治作物种子的靶标真菌病害，并对植株保持长期的防治效果。除可作为拌种剂之外，灭菌唑还可进行茎叶喷雾，持效期长达4-6周，能够防治草地早熟褐斑病。

理化性质

灭菌唑为白色粉状固体，无味（20℃），熔点为139°C~140.5°C，沸点前分解，蒸汽压小于1×10^-5 mPa （50℃），正辛醇水分配系数KowlogP = 3.29（20℃，pH=7.0），密度为1.326~1.369（20℃）。其溶解度在水中为9.3mg/L（20℃）；稳定性方面，在180°C时轻微分解。

毒性

灭菌唑原药属于低毒农药，大鼠急性经口LD50(雄/雌) > 2000 mg/kg，大鼠急性经皮LD50(雌/雄)> 2000 mg/kg，大鼠急性吸入毒性LC50(雌/雄) > 5.6mg/L。对鸟类、蜜蜂及水生动植物鱼类、藻类和溞类的急性毒性为低毒或中毒。

专利情况

灭菌唑是由德国拜耳公司于1988年研制的三唑类杀菌剂，于1993年首次在法国取得登记，后授权德国巴斯夫公司在欧洲等地销售。目前该产品已覆盖欧洲绝大多数国家，并进入阿根廷、澳大利亚、巴西、加拿大、哈萨克斯坦、巴基斯坦、南非、突尼斯、土耳其、美国和中国等市场。罗纳·普朗克农业化学公司于1989年12月29日申请灭菌唑专利（专利号：CN1031971C），目前该专利保护期已届满。

生物活性

Triticonazole 是一种三唑类农药，具有干扰内分泌作用。其靶点主要为真菌。

合成方法

以二甲基环戊酮为起始原料，与对氯苯甲醛缩合；再与碘代三甲基亚砜（由碘甲烷与二甲基亚砜制得)反应生成取代的环氧丙烷；最后与三唑反应处理即得灭菌唑。反应式如下：

[ \text{反应方程式} ]

参考资料

1. 李美霞, 陈香华, 周长勇等. 灭菌唑与氰烯菌酯复配对水稻恶苗病菌的抑制活性[J]. 农药学学报, 2022, 24: 1547-1551.
2. 陈柏. 28%灭菌唑悬浮种衣剂在玉米和土壤中的残留研究[J]. 世界农药, 2021, 43: 38-42.
3. 郑媛. 杀菌剂抑霉唑、灭菌唑诱导的烟曲霉抗药性及抗性机理[D]. 浙江大学, 2017.
4. 廖朝选, 张清海, 杨鸿波等. 灭菌唑对日本鹌鹑的急性毒性评价[J]. 贵州科学, 2014, 32: 65-68.
5. MONICA KAM DRASKAU . In vitro and in vivo endocrine disrupting effects of the azole fungicides triticonazole and flusilazole[J]. Environmental Pollution, 2019, 255: Article 113309. DOI:10.1016/j.envpol.2019.113309

反应信息

• 作为反应物：
  描述：

  硫化氢 、 Triticonazole 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 为溶剂， 生成 2-(4-chloro-benzylidene)-5,5-dimethyl-1-(5-mercapto-1,2,4-triazol-1-yl-methyl)-cyclopentan-1-ol
  参考文献：
  名称：

  Thiocyano- triazolyl derivatives and their use as microbicides

  摘要：

  本发明提供了新型硫氰酸盐-三唑基衍生物、其酸盐和金属盐络合物；它们的制备方法；以及它们作为微生物杀菌剂的应用方法。

  公开号：

  US06166059A1

文献信息

• N-ARYLAMIDINE-SUBSTITUTED TRIFLUOROETHYL SULFIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
  申请人：BAYER CROPSCIENCE AG

  公开号：US20140315898A1

  公开（公告）日：2014-10-23

  The present invention relates to novel N-arylamide-substituted trifluoroethyl sulfide derivatives of the formula (I) in which X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , n have the meanings given in the description—to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation

  本发明涉及公式（I）中的新型N-芳酰胺取代三氟乙基硫醚衍生物，其中X1、X2、X3、X4、R1、R2、R3、n的含义如描述所示—它们作为杀螨剂和杀虫剂用于控制动物害虫，并涉及其制备的过程和中间体。
• MICROBIOCIDAL PYRAZOLE DERIVATIVES
  申请人：Syngenta Participations AG

  公开号：US20150031541A1

  公开（公告）日：2015-01-29

  Compounds of the formula (I) wherein the substituents are as defined in claim 1 , are useful as a pesticides.

  公式（I）中的化合物，其中取代基如权利要求1中所定义，可用作农药。
• [EN] MICROBIOCIDAL PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLE MICROBICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013127808A1

  公开（公告）日：2013-09-06

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, are useful as a pesticides.

  公式（I）中的化合物，其中取代基如权利要求1中定义，可用作杀虫剂。
• [EN] MICROBICIDAL HETEROCYCLES<br/>[FR] HÉTÉROCYCLES MICROBICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2012069633A1

  公开（公告）日：2012-05-31

  Compounds of the formula I Formula (I) wherein the substituents are as defined in claim 1, are useful as active ingredients, which have microbiocidal activity, in particular fungicidal activity.

  式I的化合物，其中取代基如权利要求1所定义的那样，作为活性成分是有用的，具有微生物杀灭活性，特别是真菌杀灭活性。
• ARYL SULFIDE DERIVATIVES AND ARYL SULFOXIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
  申请人：BAYER CROPSCIENCE AKTIENGESELLSCHAFT

  公开号：US20160145235A1

  公开（公告）日：2016-05-26

  The present invention relates to aryl sulphide and aryl sulphoxide derivatives, to the use thereof as acaricides and insecticides for controlling animal pests and to processes and intermediates for preparation thereof. The aryl sulphide and aryl sulphoxide derivatives have the general structure (I) in which the respective radicals are as defined in the description.

  本发明涉及芳基硫醚和芳基亚砜衍生物，其用作杀螨剂和杀虫剂，用于控制动物害虫，并涉及其制备的过程和中间体。芳基硫醚和芳基亚砜衍生物具有一般结构（I），其中各自的基团如描述中所定义。