Metalaxyl 甲霜灵

甲霜灵

农药名称 甲霜灵
英文通用名称 metalaxyl
化学名称 D,L-N-(2,6-二甲基苯基)-N-(z'-甲氧苯乙酰)丙氨酸甲酯
CAS号 57837-19-1
分子式 C15H21NO4
分子量 279.33
其他名称 阿普隆、保种灵、瑞毒霉、瑞毒霜、甲霜安、雷多米尔、氨丙灵
类型：属于酰胺类杀菌剂

物化性质
本品为白色粉末。工业品熔点为63.5～72.30，沸点295.9℃(101kPa)。25℃时蒸气压为0.75mPa。密度1.20(20℃)。溶解度(25℃)：水中8.4g/L(22℃)，丙酮中450g/L，乙醇中400g/L，甲苯340g/L，正己烷11g/L，辛醇68g/L。在300℃以下稳定，室温下在中性和酸性介质中稳定。水解(20℃)DT50(计算值)>200天(pH1)，115天(pH9)，12天(pH10)。不易燃，不爆炸，无腐蚀性。

农药简介
毒性
属于低毒性杀菌剂。原药大鼠急性经口LD50为669毫克/公斤,急性经皮LD50>3100毫升/公斤。对眼睛和皮肤有轻度刺激作用，对鱼类低毒，鳟鱼TLM为100毫克/公斤(96h)。
剂型
5%颗粒剂，25%可湿性粉剂，35%拌种剂，50%瑞毒霉加铜可湿性粉剂，58%瑞毒霉锰锌粉剂等。
特点
核糖体RNA Ⅰ的合成抑制剂。内吸性杀菌剂，具有保护和治疗作用，可被植物的根茎叶吸收，并随之物体内水分运输，而转移到植物的各器官。有双向传导性能，持效期10-14天，土壤处理持效期可超过2个月。

适用范围
对霜霉病菌、疫霉病菌和腐病菌引起的多种作物霜霉病，瓜果蔬菜类的疫霉病、谷子白发病有效。

使用方法
1、一般用25%WP750倍液，防治黄瓜霜霉病和疫病，茄子、番茄及辣椒的棉疫病，十字花科蔬菜白锈病等，每隔10-14天喷1次，用药次数每季不得超过3次。
2、谷子白发病的防治 每100公斤种子用35%拌种剂200-300克拌种，先用1%清水或米汤将种子湿润，再拌入药粉。
3、烟草黑茎病的防治 苗床在播种后2-3天，每亩用25%可湿性粉剂133克，进行土壤处理，本田在移栽后第7天用药，每亩用58%可湿性粉剂兑水500倍喷雾。
4、马铃薯晚疫病的防治 初见叶斑时，每亩用25%可湿性粉剂500倍液喷雾，每隔10-14天喷1次，不得超过3次。

注意事项
单一长期使用该药，病菌易产生抗性。

生产方法
在碳酸氢钠存在下，将2,6-二甲基苯胺与2-溴丙酸甲酯反应，制得DL-N-(2,6-二甲基苯基)-α-氨基丙酸甲酯。再用甲氧基乙酰氯进行酰化反应，即得甲霜安。
具体制备方法如下：
1、α-氯代丙酸甲酯的制备：氯代丙酸与甲醇直接酯化，浓硫酸为催化剂，加无水氯化钙为脱水剂。在50～60℃搅拌反应8h。上层粗酯加水，并用Na2CO3调节pH值为6。分离水相后蒸馏得α-氯代丙酸甲酯，含量97.7%，收率91.8%。
也可采用光气与α-氯代丙酸作用，生成α-氯代丙酰氯，再与甲醇反应制得α-氯代丙酸甲酯。
2、2,6-二甲苯胺的制备 将间二甲苯用混酸(HNO3+H2SO4)硝化，分离副产物2，4-二甲基硝基苯，制得2，6-二甲基硝基苯。然后用氢气还原得2，6-二甲基苯胺。
甲氧基乙酸的制备：乙二醇-甲醚用硝酸氧化，催化剂为钒盐和铜盐，于60～70℃搅拌1h，80～90℃搅拌3h，再升温至90～100℃，加入37%甲醛溶液，回流搅拌1h后结束反应，蒸去130℃以下馏分，减压收集甲氧基乙酸，含量96.7%，收率86.8%。
3、甲氧基乙酸的制备：乙二醇－甲醚用硝酸氧化，催化剂为钳盐和铜盐，于60～70℃搅拌1h、80～90℃。
消耗定额/(t/t)：
丙酸 0.87
2,6-二甲基苯胺 0.84

分析方法
气相色谱法分析：气相色谱仪带有火焰离子化检测器(FID)，色谱柱1.0m×0.003m(内径)的玻璃柱，内装涂有10%SE-30固定液的载体Chromosozb W AW DMCS 60～80目。柱温180℃，气化室温度240℃，检测室温度240℃。载气(N2)流速40ml/分钟，氢气流速40ml/分钟，空气500ml/分钟。内标物：十八碳烷无干扰杂质。上述色谱条件下，保留时间：本品约7.5分钟，十八碳烷约5.5分钟。

包装贮运
原药用镀锌铁桶包装，每桶净重50kg；各类制剂用40(内径)×54cm的硬纤维板圆桶包装，每桶内装200包(双层塑料袋)，每包100g，每桶净重20kg。贮运严防潮湿和日晒，保持通风良好，并不要与食品、饲料混放，贮存温度不得超过35℃。贮藏于通风阴凉干燥处。本品无特效解毒剂，只要对症治疗。

metalaxyl
Fungicide
FRAC 4, A1; phenylamide: acylalanine

NOMENCLATURE
Common name metalaxyl (BSI, E-ISO, (m) F-ISO, ANSI)
IUPAC name methyl N-(methoxyacetyl)-N-(2,6-xylyl)-DL-alaninate; methyl 2-{[(2,6-dimethylphenyl)methoxyacetyl]amino}propionate
Chemical Abstracts name methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate
CAS RN [57837-19-1] EEC no. 260-979-7 Development codes CGA 48 988 (Ciba-Geigy)

PHYSICAL CHEMISTRY
Mol. wt. 279.3 M.f. C15H21NO4 Form Fine, white powder. M.p. Tech. 63.5-72.3 ºC B.p. 295.9 °C/101 kPa V.p. 0.75 mPa (25 ºC) KOW logP = 1.75 (25 ºC) Henry 1.6 ´ 10-5 Pa m3 mol-1 (calc.) S.g./density 1.20 at 20 ºC Solubility In water 8.4 g/l (22 ºC). In ethanol 400, acetone 450, toluene 340, n-hexane 11, n-octanol 68 (all in g/l, 25 ºC). Stability Stable up to 300 ºC. Stable in neutral and acidic media at room temperature; on hydrolysis, DT50 (calc.) (20 ºC) >200 d (pH 1), 115 d (pH 9), 12 d (pH 10). pKa <<0

COMMERCIALISATION
History Fungicide reported by F. J. Schwinn et al. (Mitt. Biol. Bundesanst. Land-Fortswirtsch. Berlin-Dahlem, 1977, 178, 145) and by P. A. Urech (Proc. 1977 Br. Crop. Prot. Conf. - Pests Dis., 1977, 2, 623). Introduced by Ciba-Geigy AG (now Syngenta AG) and first marketed in 1979. Patents BE 827671; GB 1500581; US 4151299 Manufacturers Agrochem; Jingma; Rallis; Sharda; Syngenta

APPLICATIONS
Biochemistry Inhibits protein synthesis in fungi, by interference with the synthesis of ribosomal RNA. Mode of action Systemic fungicide with protective and curative action, absorbed through the leaves, stems, and roots. Uses To control diseases caused by air- and soil- borne Peronosporales on a wide range of temperate, subtropical and tropical crops. Foliar sprays with mixtures of metalaxyl and protectant fungicides are recommended to control air-borne diseases caused by Pseudoperonospora humuli on hops, Phytophthora infestans on potatoes and tomatoes, Peronospora tabacina on tobacco, Plasmopara viticola on vines, Bremia lactucae on lettuce, and downy mildews on various vegetables, at 200-300 g/ha. Soil applications of metalaxyl alone are used to control soil-borne pathogens causing root and lower stem rots on avocado and citrus, at 500-1500 g/ha. Seed treatments control systemic Peronosporaceae on maize, peas, sorghum and sunflowers, as well as damping-off (Pythium spp.) of various crops. Formulation types DS; FS; GR; WP. Selected products: 'Ridomil' (Syngenta); 'Duet' (Devidayal); 'Metamix' (Agrimix); 'Vacomil-5' (Vapco); 'Vilaxyl' (Vipesco); mixtures: 'Maxim' (+ fludioxonil) (seed treatment) (Syngenta); 'Hawaii' (+ mancozeb) (Rocca); 'Milor' (+ mancozeb) (Rotam); 'System 3' (+ quintozene+ Bacillus subtilis) (Crompton, Helena); 'Talman-combi' (+ mancozeb) (Cequisa)

OTHER PRODUCTS
'Apron' (Syngenta); 'Subdue' (Syngenta); 'Allegiance' (Gustafson); 'Armetil 5G' (IQV); 'Axanit' (Nitrokémia); 'Cure-Plus' (Agrochem); 'Otria 5G' (Probelte); 'Pilarxil' (Pilarquim) mixtures: 'Favour' (+ thiram) (Syngenta); 'Folio' (+ chlorothalonil) (Syngenta); 'Maxim Apron' (+ fludioxonil) (Syngenta); 'Ridomil Copper 70W' (+ copper hydroxide) (Syngenta); 'Ridomil mbc' (+ carbendazim) (Syngenta); 'Ridomil MZ' (+ mancozeb) (Syngenta); 'Ridomil PC' (+ quintozene) (Syngenta); 'Ridomil Plus' (+ copper oxychloride) (Syngenta); 'Agrox Premiere' (+ captan+ diazinon+ gamma-HCH) (Agriliance); 'Armetil 50' (+ folpet) (IQV); 'Armetil Cobre' (+ copper oxychloride) (IQV); 'Armetil M' (+ mancozeb) (IQV); 'Armetil Triple' (+ copper oxychloride+ folpet) (IQV); 'Cure-M' (+ mancozeb) (Agrochem); 'Fortiva' (+ thiabendazole+ thiram) (seed) (Limagrain); 'Gaucho XT' (+ tebuconazole+ imidacloprid) (Gustafson); 'Kodiak A-T' (+ quintozene) (Gustafson); 'Metamac' (+ mancozeb) (AgroSan); 'Metasan' (+ mancozeb) (Dow AgroSciences); 'Otria Plus' (+ mancozeb) (Probelte); 'Raxil MD Extra' (+ tebuconazole+ imazalil) (Gustafson); 'Sanchar' (+ mancozeb) (Biostadt); 'Stiletto' (+ thiram+ carboxin) (Trace); 'Tachigare-Ace' (+ hymexazol) (Sankyo Agro); 'Vacomil Mz-72' (+ mancozeb) (Vapco); 'Vacomil Plus' (+ copper oxychloride) (Vapco); 'Vimonyl' (+ mancozeb) (Vipesco); 'Viroxyl' (+ copper oxychloride) (Vipesco) Discontinued products: 'Polycote Universal' * (Seedcote) mixtures: 'Apron Combi' * (+ thiabendazole+ thiram) (seed) (Novartis); 'Fubol' * (+ mancozeb) (Syngenta); 'Osprey' * (+ mancozeb) (Novartis); 'Agromil MZ' * (+ mancozeb) (Agro Chemicals); 'Agromil Plus' * (+ copper oxychloride) (Agro Chemicals); 'Agroxyl M' * (+ mancozeb) (Agrochem); 'Chloraxyl' * (+ chloroneb) (Micro Flo)

ANALYSIS
Product analysis by glc (CIPAC Handbook, 1992, E, 123-130). Residues in plants and soil determined by glc with TID (D. J. Caverley & J. Unwin, Analyst (London), 1980, 106, 389).

MAMMALIAN TOXICOLOGY
Reviews FAO/WHO 38, 39 (see part 2 of the Bibliography). Oral Acute oral LD50 for rats 633, mice 788, rabbits 697 mg/kg. Skin and eye Acute percutaneous LD50 for rats >3100 mg/kg. Slight irritant to eyes; not irritant to skin of rabbits. No skin sensitisation (guinea pigs). Inhalation LC50 (4 h) for rats >3600 mg/m3. NOEL for rats 2.5, mice 35.7, dogs 8.0 mg/kg b.w. daily. ADI (JMPR) 0.03 mg/kg b.w. [1982]; (Syngenta) 0.025 mg/kg b.w. Other Not oncogenic, not mutagenic, not teratogenic. Toxicity class WHO (a.i.) III EC classification (Xn; R22, R52)

ECOTOXICOLOGY
Birds LD50 for Japanese quail (7 d) 923, mallard ducks (8 d) 1466 mg/kg. LC50 (8 d) for Japanese quail, bobwhite quail and mallard ducks >10 000 mg/kg. Fish LC50 (96 h) for rainbow trout, carp, and bluegill sunfish >100 mg/l. Daphnia LC50 (48 h) >28 mg/l. Algae IC50 (5 d) for Scenedesmus subspicatus 33 mg/l. Other aquatic spp. EC50 (96 h) for mysid shrimp (Mysidopsis bahia) 25, Eastern oyster (Crassostrea virginica) 4.6 mg/l. Bees Not toxic to bees. LD50 (48 h) (contact) >200 mg/bee; (oral) 269.3 mg/bee. Worms LC50 (14 d) for Eisenia foetida >1000 mg/kg soil. Other beneficial spp. Harmless to Poecilus cupreus and Coccinella septempunctata (IOBC).

ENVIRONMENTAL FATE
Animals In mammals, following oral administration, metalaxyl is rapidly absorbed and also rapidly and almost completely eliminated with urine and faeces. Metabolism proceeds via hydrolysis of the ester bond, oxidation of the 2-(6)-methyl group and of the phenyl ring and N-dealkylation. Residues in tissues were generally low and there was no evidence for accumulation or retention of metalaxyl or its metabolites. Plants Metalaxyl is metabolised by more than 4 types of phase I reaction to form eight metabolites; at phase II, most of the metabolites are sugar conjugated. The types of reaction in phase I are: oxidation of the phenyl ring, oxidation of the methyl group, cleavage of the methyl ester and N-dealkylation. Soil/Environment In soil, DT50 29 d (realistic range 10-40 d), Koc 70 ml/g (realistic range 30-300 ml/g). DT50 in water 22-48 d. Photolytically stable in water and on soil surfaces.