Ametoctradin: Chemical Profile and Agricultural Role, and Industrial Data

Ametoctradin: Chemical Profile and Agricultural Role, and Industrial Data

Chemical structure: Ametoctradin is 5-ethyl-6-octyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine, a white odourless crystalline solid. Its molecular formula is C₁₅H₂₅N₅ (MW 275.40), CAS 865318-97-4. The molecule features a fused 1,2,4-triazole–pyrimidine ring bearing an ethyl substituent at N-5, an octyl chain at C-6, and a C-7 amino group. It is essentially non-volatile (vapor pressure ≈2.1×10⁻¹⁰ Pa at 20 °C) and poorly water-soluble (log K_OW ≈4.4). The compound melts at ~197–198 °C and is hydrolytically stable in water. In soil, ametoctradin adsorbs very strongly (K_OC ≈3.9×10³ L/kg), giving it an aerobic soil half-life on the order of days (~11.9 d) and minimal leaching potential. Degradation in anaerobic soils can take much longer (months), and although parent ametoctradin is immobile to groundwater, some polar degradates may persist.

Synthesis: Ametoctradin (development code BAS 650F) was developed by BASF via multi-step heterocycle synthesis (patents describe cyclization routes to substituted [1,2,4]triazolopyrimidines). The technical product is made by organic condensation reactions (often starting from appropriate 5-ethyl-1,2,4-triazole precursors and alkyl halides) under proprietary conditions. (Exact synthetic methods are documented in BASF patents and regulatory dossiers but are beyond scope here.) The technical grade active ingredient is supplied at >97% purity, typically as BASF’s BAS 650F or Initium.

Agricultural Uses and Formulations

Ametoctradin is a post-emergence fungicide specifically active against oomycete pathogens (downy mildews and Phytophthora spp.). It is labeled on a wide range of crops, particularly vegetables and fruits. Major uses include control of downy mildew and late blight on potatoes, lettuce and other leafy vegetables, bulb crops (onions, garlic), brassicas (cabbage, broccoli), cucurbits (cucumber, melon), fruiting vegetables (tomatoes, peppers), wine grapes, hops, and ornamentals. For example, BASF’s Zampro (a 26.9% SC premix of ametoctradin + dimethomorph) is registered on potato, grape, hop and various vegetable crops. Orvego (ametoctradin + dimethomorph) targets downy mildew and Phytophthora on ornamentals. Health Canada’s 2011 registration summary similarly approves Ametoctradin (BAS 650F) on brassica leafy vegetables, bulb and cucurbit vegetables, fruiting and leafy vegetables, hops, grapes and potatoes, specifically for downy mildew, late blight, and Phytophthora blight. In practice it is often applied preventively, as a spray or drench: soil-drench and foliar applications are both effective (it is translaminar and locally systemic). Labels typically limit it to a few applications per season (e.g. 2–3 sprays) and recommend tank-mix or rotation with other modes of action for resistance management.

Formulations: Ametoctradin is sold only as a formulated product (no granular or seed treatments). Examples include suspension concentrates (e.g. BAS 650 00 F) and SC premixes (Zampro, Orvego). The chemical’s low water solubility and polarity require surfactant carriers. As a technical active, BASF markets the pure Ametoctradin (BAS 650F, as technical powder) and trade name Initium. Most end-user products are co-formulated (notably with dimethomorph) to broaden spectrum.

Mode of Action (Molecular Target)

Ametoctradin’s fungicidal activity stems from inhibition of mitochondrial Complex III (cytochrome bc₁ complex) in oomycetes. It is classified by the Fungicide Resistance Action Committee (FRAC) as Group 45 (“QoSI”, quinone outside inhibitor), although its binding site overlaps both the Q₀ and Qᵢ sites. The compound binds the Qi site of cytochrome b, blocking electron transport and ATP synthesis in the fungal mitochondria. This energy blockade rapidly disrupts zoospore development and germination: for example, ametoctradin “strongly inhibits zoospore differentiation, release, motility and germination” in Downy Mildew pathogens. BASF notes that treated zoospores will often “burst within seconds” of exposure. In effect, ametoctradin cuts off the energy flow in the pathogen, rendering it incapable of host infection.

Cellularly, ametoctradin is mainly a locally systemic (translaminar) protectant fungicide. After uptake, it translocates into treated leaves and roots, but does not readily move to untreated tissues, so it is not fully systemic. It exhibits some curative activity on very young lesions, but is most effective as a protective barrier. Because of its unique target (Site Qi of Complex III), ametoctradin has no cross-resistance with older groups like phenylamides (FRAC 4) or QoI fungicides (FRAC 11). However, cross-sensitivity effects have been noted in mutants (see below). In practical terms, its mode class (triazolopyrimidine) is distinct from azole demethylation inhibitors or from conventional strobilurins (QoI), which is why it is often combined with dimethomorph (a Group 40 cell-wall inhibitor) in products to provide multi-site control.

Production, Manufacturers, and Global Use

Ametoctradin was developed and is produced by BASF SE (Ludwigshafen, Germany), a leading agrochemical company. BASF holds the patents and regulatory registrations for BAS 650F. Globally, BASF and its local affiliates (e.g. BASF Corporation in USA, BASF India Ltd., etc.) are the principal suppliers. The technical active is manufactured in BASF facilities in Europe (Limburgerhof, Germany) and shipped for formulation worldwide. No other major manufacturer has licensed or commercialized Ametoctradin as an active ingredient.

The compound has been registered in all major agricultural markets: in the European Union (member states such as France, Germany, Hungary, Estonia, UK, etc. as of 2011); in the United States (EPA registrations for BAS 650 00 F and for Zampro/Orvego, first approved 2012); in Canada (Pest Management Regulatory Agency approved in 2012); Australia (approved 2013); and in Latin American and Asian countries (Argentina, Chile, Columbia, Korea, Turkey, etc. listed in APVMA report). BASF markets it under names like BAS 650 00 F (technical or SC concentrate), Initium, and in premixes Zampro and Orvego.

Economically, ametoctradin is considered a high-value specialty fungicide. While BASF does not report sales by compound, it is part of BASF’s crop protection portfolio, which is a multi-billion-Euro business. For context, BASF’s Agricultural Solutions segment recorded ~€9.8 billion in sales in 2024. The global fungicide market was about US$21.2 billion in 2024 (projected to ~$32 billion by 2032). Within this market, Ametoctradin occupies a niche as a premium oomycete-control agent on high-value crops. Products like Zampro/Orvego command premium prices, justified by their broad spectrum and resistance-management benefits. (BASF’s stock is traded publicly, and crop protection is a key part of its Ag Solutions segment, but Ametoctradin is only one of many active ingredients in the portfolio.)

Resistance and Genetics

As with all single-site fungicides, there is concern about target-site resistance. Laboratory and field studies have identified point mutations in the cytochrome b gene of oomycetes that confer resistance to ametoctradin. In Phytophthora sojae (soybean blight), for example, resistant lab mutants uniformly harbored a S33L substitution in PsCytb. Similarly, in Phytophthora litchii (lychee downy blight), two resistance mutations were found: S33L and D228N in the PlCytb gene. In these mutants, ametoctradin EC₅₀ values were >400× higher than wild type. Notably, the S33L mutation often led to cross-sensitivities: strains with S33L became unusually sensitive to traditional QoI (azoxystrobin) and to ametoctradin’s analog amisulbrom, whereas the D228N mutation conferred sensitivity to cyazofamid (a Qi-site fungicide).

Field monitoring in Plasmopara viticola (grapevine downy mildew) has likewise detected ametoctradin resistance. Starting around 2015, a S34L substitution in the cytochrome b gene (equivalent to S33L in other numbering) was found in some European isolates. In these populations, resistance remains rare; most control failures are currently due to increased expression of alternative oxidase (AOX) enzymes, which bypass Complex III and reduce ametoctradin’s effectiveness. The studies note that the S34L allele frequency is still low, suggesting a fitness penalty for the mutant. However, AOX-based resistance is becoming more common and can undermine all Complex III inhibitors.

To date, no cross-resistance has been observed between ametoctradin and other fungicide classes (e.g. it still works on QoI- or phenylamide-resistant isolates). Nonetheless, the appearance of Cytb mutants means that stewardship is vital: label directions emphasize alternating Ametoctradin with unrelated modes (e.g. cyazofamid or mancozeb) and limiting to 2–3 applications per season. Resistance management also exploits the observed fitness cost: for instance, mix programs can exploit the fact that ametoctradin-resistant strains may be compromised in sporulation relative to wild types.

Fungicides Comparable to Ametoctradin

Ametoctradin (FRAC Group 45) is one of many modern fungicides grouped by mode of action. Table 1 below lists 50 representative fungicides (“best-known” in crop protection), organized by their FRAC molecular target group and practical use pattern (systemic vs protectant, curative vs preventive). This illustrates how different chemical families (triazoles, strobilurins, SDHIs, multi-site protectants, etc.) compare to ametoctradin’s profile. (FRAC group names are given where standardized; specialization terms systemic, contact/protectant, curative refer to their primary activity.)

 

Selected fungicides related by mode of action or use (names are common names unless noted).

Fungicide (example)	FRAC Group / MoA	Application Type / Specialization
Demethylation Inhibitors (DMIs)
Tebuconazole	3 (SBI, DMI; azole)	Systemic, translaminar (protectant)
Propiconazole	3 (DMI)	Systemic
Difenoconazole	3 (DMI)	Systemic
Flutriafol	3 (DMI)	Systemic
Myclobutanil	3 (DMI)	Systemic
Quinone Outside Inhibitors (QoIs)
Azoxystrobin	11 (QoI, strobilurin)	Systemic, protectant (curative)
Pyraclostrobin	11 (QoI)	Systemic, protectant/curative
Trifloxystrobin	11 (QoI)	Systemic
Kresoxim-methyl	11 (QoI)	Systemic
Fenamidone	11 (QoI, oxazole)	Systemic
Picoxystrobin	11 (QoI)	Systemic
SDH Inhibitors (SDHIs)
Boscalid	7 (SDHI, carboxamide)	Systemic
Bixafen	7 (SDHI)	Systemic
Fluopyram	7 (SDHI)	Systemic
Penthiopyrad	7 (SDHI)	Systemic
Isopyrazam	7 (SDHI)	Systemic
Phenylamides (PAs)
Metalaxyl (Mefenoxam)	4 (PMA)	Systemic
Carboxamides (SDHI class)
Carboxin	7 (SDHI)	Systemic
Moropholines / Morpholines
Dimethomorph	40 (MDI, morpholine)	Systemic (root and foliar)
Fenpropimorph	40 (MDI)	Systemic
Mandipropamid	40 (MDI, also pyridyl)	Systemic
Cytochrome bc₁ inhibitors (Qi-site)
Cyazofamid	21 (QI fungicide)	Systemic
Amisulbrom	21 (QI)	Systemic
Phenylpyrroles
Fludioxonil	12 (PP, fludioxonil)	Contact protectant (also inhibits spore germination)
Multi-site Protectants (M) and Contact
Chlorothalonil	M03 (multi-site)	Contact protectant (broad-spectrum)
Mancozeb	M03 (multi-site)	Contact protectant (broad-spectrum)
Metiram	M03 (multi-site)	Contact protectant
Folpet	M04 (multi-site)	Contact protectant
Copper hydroxide	M01 (multi-site metal)	Contact protectant
Propineb	M03 (multi-site)	Contact protectant
Dicarboximides
Iprodione	2 (Dicarboximide)	Systemic (protectant/curative for foliar diseases)
Procymidone	2 (Dicarboximide)	Systemic
Benzimidazoles (MBCs)
Carbendazim	1 (MBC)	Systemic (broad-spectrum, seed treatment)
Thiabendazole	1 (MBC)	Systemic (seed treatment, storage)
Thiophanate-methyl	1 (MBC)	Systemic
Amine Inhibitors (APs)
Pyrimethanil	9 (AP, anilinopyrimidine)	Systemic (leaf-surface)
Cyprodinil	9 (AP)	Systemic
Microbial & Miscellaneous
Oxathiapiprolin	U15 (piperidinyl thiazole)	Systemic (oomycete-specific)
Fluopicolide	43 (pyridine N-oxide)	Systemic (unknown target)
Zoxamide	22 (benzamide)	Systemic
Iprovalicarb	28 (valinamide carbamate)	Systemic
Phosphorous acid (Fosetyl-Al)	33 (phosphonate)	Systemic (induces host resistance + partial pathogen control)
Polyoxin D	28 (heptaene nucleoside)	Systemic (chitin synthesis inhibitor, for specific crops)
Validamycin A	28 (imidazole ammonium salt)	Systemic (trehalase inhibitor, used in rice)
Triadimefon	3 (DMI)	Systemic
Triadimenol	3 (DMI)	Systemic
Propineb	M03 (multi-site)	Contact
Special Case
Ametoctradin (for reference)	45 (QoSI, triazolopyrimidine)	Translaminar systemic (zoospore killer)

Here are the known bioreactor and formulation facilities involved in the production of Ametoctradin (as part of BASF’s manufacturing infrastructure):

• Ludwigshafen, Germany

  • BASF’s central site for both chemical manufacturing and fermentation-based production. This site oversees the synthesis of technical Ametoctradin (BAS 650F) and is expanding in biological production via a new fermentation plant (operational by late 2025) for biotech active ingredients (agrospectrumasia.com).

• Tarragona, Spain

  • Hosts a major fungicide formulation and packaging plant. In late 2016, BASF expanded this site with a fifth formulation line—handling products like Zampro/Enervin—boosting capacity by ~25% (agriculture.basf.us).

• Rudong (Yangkou Industrial Park), Jiangsu, China

  • BASF’s first formulation and packaging facility in China, commissioned in August 2014, with ~10,000 t annual capacity across crop protection products including fungicides (agriculture.basf.us).

• Guaratingueta, Sao Paulo, Brazil

  • A chemical complex ~170 km from São Paulo. Since mid‑2013, BASF has been expanding fungicide production here, including formulation of various actives (not necessarily only Ametoctradin) to serve Latin American markets (process-worldwide.com).

These facilities collectively form BASF’s global production network for Ametoctradin and its formulated products. They include both chemical synthesis (bioreactor/fermentation) and formulation/packaging locations tailored for regional markets.

Most genetic mutations that are the reason for fungal resistance to Ametoctradin are found the cytochrome b (Cytb).

Here is a small list of some organisms with documented reduced sensitivity / resistance to ametoctradin

1. Plasmopara viticola (grapevine downy mildew) — target-site mutation S34L and AOX overexpression reported; single-case target-site resistance first detected ~2015; non-target (AOX) resistance also documented.

2. Phytophthora sojae (soybean root and stem rot / Phytophthora root rot) — laboratory and molecular work identifies PsCytb S33L mutation conferring ametoctradin resistance; confirmed by ectopic overexpression studies.

3. Phytophthora litchii (litchi Phytophthora / litchi downy/blight-type infections) — mutations S33L and D228N in Cytb implicated in reduced sensitivity to ametoctradin.

4. Phytophthora spp. (other Phytophthora species) — laboratory reports and field monitoring indicate reduced sensitivity/selection under pressure in several Phytophthora species (reports vary by species and region).

5. Pseudoperonospora spp. (including Pseudoperonospora cubensis — cucurbit downy mildew) — reduced sensitivity to various oomycete-active fungicides (and rapid emergence of resistant clades) has been reported; ametoctradin mixes are used but sensitivity can vary by clade and region, and selection for reduced sensitivity has been observed in field populations.