Soaps, detergents and agrochemicals: Making, formulating and selling pesticides

5.1 Making an active: 2,4-D in four reactions

Pesticide synthesis is typically multi-step, and Kent lists what decides the route: price and availability of raw materials, the reactions the plant can handle, the impurity profile, yield and purity at each stage, the effluent produced, and whether someone holds a patent on the process.

2,4-D, the phenoxy herbicide that Shreve says ignited the modern herbicide market, makes a good worked example because both Shreve and Dryden describe it. It is built from two pieces, each made from a basic chemical. Phenol is chlorinated to 2,4-dichlorophenol and distilled. Acetic acid is chlorinated to monochloroacetic acid. Both consume Chlorine: Dryden shows Indian pesticides taking 38,000 tonnes in 1990, 38 / 541 = 7% of national use.

The coupling happens in water. In an agitated, jacketed steel reactor, dichlorophenol is converted to its sodium salt with caustic soda, and chloroacetic acid is likewise neutralised. The phenoxide then displaces chloride from the chloroacetate: Cl₂C₆H₃ONa + ClCH₂COONa → Cl₂C₆H₃OCH₂COONa + NaCl. The reaction gives off heat and runs at 60-80 C for 6-8 hours. Hydrochloric acid in an enamel-lined tank frees the acid. A brick-lined steam still strips volatile impurities, and the product is filtered and dried to crystals.

The acid is rarely sold as such: Shreve notes it is usually used as an amine salt or ester to reduce volatility.

Dryden's engineering notes are mostly about the environment. Waste disposal needs great care: one plant grew test tomato plants within a two-mile radius to detect airborne herbicide, and sent aqueous wastes to biological treatment. For the organophosphate parathion, reactors stood in concrete cubicles with three walls and no roof, to vent rather than confine an explosion if the exothermic reaction ran away.

• Kent (2012), Ch 17 The Agrochemical Industry · pdf p. 668
• Shreve (1984), Ch 26 Agrichemical Industries · pdf pp. 492-493
• Dryden (1997), IVG Pesticides · pdf pp. 558-563
• Dryden (1997), IIH Chlor-Alkali Industry · pdf p. 207

5.2 Formulation turns a technical active into something a farmer can spray

The technical material from the plant is seldom used as it is. Kent explains that it is mixed with solvents, surfactants and carriers into a formulation that stores well and works once diluted.

Four formats cover much of the market. An emulsifiable concentrate (EC) dissolves the active in a solvent with emulsifiers; poured into the spray tank it turns milky as fine oil droplets form. ECs are easy to make and mix and suit water-insoluble, low-melting actives, but Kent lists their drawbacks: cold-weather crystallisation, possible crop damage, higher skin toxicity and costly packing and shipping. A wettable powder (WP) carries the active on a mineral powder; it is cheap and solvent free but dusty. Granules (GR) are ready to use: active on a carrier, applied to soil or paddy, with low drift and long residual action, though birds may eat them. A suspension concentrate (SC) mills a solid active into fine particles suspended in water with thickener and antifreeze; it avoids solvent and dust and allows high loadings, but it is hard to make stable, can settle and cake, and is sensitive to freezing and to the crystal form of the active.

Newer formats avoid solvent and dust: water-dispersible granules, emulsions in water and slow-release capsule suspensions. Seed coatings put the active exactly where it is needed; Kent reports the seed treatment market growing from about $900 million in 2001 to $2.5 billion in 2009.

Spraying is wasteful. Kent quotes efficiencies of 80% for deposition on the leaf, 50% retention, 50% uptake and 10% movement to the site of action: 0.8 x 0.5 x 0.5 x 0.1 = 0.02, so no more than about 2% of a systemic spray reaches its target. Adjuvants such as spreaders, stickers and penetrants, many of them Surfactants, aim to raise those numbers.

• Kent (2012), Ch 17 The Agrochemical Industry · pdf pp. 669-673, 676
• Dryden (1997), IVG Pesticides · pdf p. 555

5.3 A few patent holders, many generic makers, and India in between

Kent sizes the global pesticide market at about $44 billion in 2009: $38 billion for crop protection (86%) and $6 billion for non-crop uses such as public health, timber, railway weed control and homes. Crop protection grew from $28.1 billion in 1999, with growth expected from Latin America, India and China.

The market divides by intellectual property. Patented products are about 30% of sales. Off-patent proprietary products, whose patents have expired but which face no generic competitor yet, take most of the rest; together the two are about 70% and are controlled by a few multinationals, which Kent names as Syngenta, Bayer CropScience, BASF, Dow AgroSciences, Monsanto, DuPont and FMC. Generics, sold by companies holding their own registrations after patent expiry, are about 30%, roughly $13 billion.

Why do generics not take over at once? Registration again. A generic maker must show that its technical material is equivalent to the reference product. Kent describes the package: acute toxicology, details of the manufacturing process, the impurity profile and analyses of five typical production batches, compared impurity by impurity with the original. If profiles differ, the authority can demand chronic and ecotoxicology data, and every country assesses separately. The barrier is far lower than for a new active but rewards clean, consistent processes.

India is a large maker of older, off-patent actives. Dryden reports production of 85,500 tonnes in 1993-94 against demand of 71,000 tonnes in 1989-90, with many actives made by several firms: monocrotophos by about nine and chlorpyrifos by six. Kent's authors, from the Indian producer Gharda Chemicals, list molecules going off patent as generic targets.

Two threats hang over margins: counterfeit product, which Kent says may be up to 40% of pesticides sold in some countries, and biotechnology, whose effect is mixed: Kent reports that insecticide use on Indian Bt cotton rose many fold to control sucking pests, while glyphosate-tolerant crops bred glyphosate-resistant weeds.

• Kent (2012), Ch 17 The Agrochemical Industry · pdf pp. 652, 673-677
• Dryden (1997), IVG Pesticides · pdf pp. 555-557

See it in the table

Check your understanding

A water-insoluble, low-melting active must be formulated simply for farmers who dilute in a spray tank. Which format fits, and what is its main drawback?

What must a generic producer show to register an off-patent active?

Shreve's trifluralin route has step yields of 95%, 83% and 96%. What is the overall yield?