Chlorinated and Fluorinated Derivatives of Methylpyridine and Their Market and Supply

Commonly used methylpyridine products are CCMP (2-chloro-5-chloromethylpyridine), 2-methylpyridine, 3-methylpyridine, and 4-methylpyridine. These four products belong to the category of pyridine, and are the methylpyridine products with the highest application value in the agrochemical industry.

In terms of the production process, there is not necessarily an upstream or downstream relationship between pyridine and various methylpyridine products. Formerly, pyridine was extracted mainly from coal tar, and now it is primarily obtained through the synthesis method. The aldehyde-ammonia method is the most common chemical synthesis method. Different pyridine compounds can be obtained based on raw material aldehyde and different reaction conditions. For example, acetaldehyde reacts with ammonia to produce pyridine, 2-methylpyridine and 4-methylpyridine; acetaldehyde, formaldehyde react with ammonia to produce pyridine, 3-methylpyridine, etc. CCMP can be obtained from the reaction of 3-methylpyridine downward or from the reaction of dicyclopentadiene (as the starting material) with acrylaldehyde or acrylonitrile.

Derivative products of methylpyridine after chlorination and fluorination

There are many derivatives of methylpyridine products after chlorination and fluorination. The specific derivation modes include adding trichloro or trifluoro in 2-6 positions of pyridine moiety; chloro, fluoro, amino, hydroxyl, bromo or iodo to 2 position; chlorio, fluoro, amino or hydroxyl to 2 and 3 positions. The derived products are 2-trifluoromethyl pyridine, 2-chloro-3-trifluoromethyl pyridine, 2-chloro-4-trichloromethyl pyridine, 2-amino-5-trifluoromethyl pyridine, 2-amino-3-chloro-5-trifluoromethyl pyridine, 2-chloro-6-trifluoromethyl pyridine, etc.

The following three figures show in detail the downstream derivatives and applications of each series of 2-methylpyridine, 3-methylpyridine and 4-methylpyridine.

1. Downstream derivatives of 2-methylpyridine

Downstream derivative of 2-methylpyridine (intermediates in blue and pesticide technicals in green)

2-chloro-6-trichloromethyl pyridine (CTC) is obtained by stepwise deep chlorination of 2-methylpyridine. CTC has a wide range of applications. For example, it can be used to produce chlorfenapyr, a pesticide with certain herbicidal activity and can control cyanobacteria in water.

CTC also has a remarkable effect in the field of nitrogen fertilizer synergists. It can inhibit or regulate the nitrification of ammonia nitrogen in the soil or other plant growth media. The consumption of nitrogen fertilizer can be reduced by 30% by adding 1kg of synergist to 1t of nitrogen fertilizer. At present, nitrogen fertilizer synergists have been widely used in developed areas abroad. The product will have a favorable market development prospect, considering its low use rate in the Chinese market.

CTC is subject to further deep fluorination produces 2-fluoro-6-trifluoromethyl pyridine (FTF). FTF is a key intermediate for the production of pesticides flupyrsulfuron-methyl-sodium, thiazopyr, dithiopyr, bicyclopyrone, sulfoxaflor, etc. 2-amino-6-trifluoromethyl pyridine can be produced by introducing ammonia gas to add amino group.

Another process route is to obtain 2-chloro-6-trifluoromethyl pyridine by fluorination of CTC, and then add the hydroxyl by introducing alkali to produce 2-hydroxy-6-trifluoromethyl pyridine (HTF). HTF can be used to produce picoxystrobin.

2. 3-methylpyridine

Downstream derivatives of 3-methylpyridine

3-methylpyridine is obtained by stepwise chlorination of 2-chloro-3-trichloromethyl pyridine, which is then fluorinated to obtain 2-chloro-3-trifluoromethyl pyridine, an intermediate for the production of flazasulfuron.

3-methylpyridine is chlorinated to 2-chloro-5-methylpyridine and further chlorinated to CCMP, which can be directly used as an intermediate of imidacloprid and acetamiprid. CCMP can also be further fluorinated and chlorinated to produce DCTF, which can be used to produce a variety of pesticides, such as haloxyfop-methyl, haloxyfop-P-methyl, haloxyfop-methyl, chlorfluazuron, and fluazuron. Ammonia gas can be introduced to DCTF to produce 2-amino-3-chloro-5-trifluoromethyl pyridine (ACTF), a key intermediate of fluazinam.

Back to 2-chloro-5-methylpyridine, it is first chlorinated and then fluorinated to obtain 2-chloro-5-trifluoromethyl pyridine (CTF), an intermediate of pyridalyl and fluazifop-butyl series products.

The downstream value of other related derivatives such as 3-trifluoromethyl pyridine and 2-amino-5-trifluoromethyl pyridine is also worth probing.

Among the thirteen pesticide technicals shown in the figure, imidacloprid is currently one of the top three highly effective new insecticides globally. Chinese companies have an annual production capacity of over 10,000 tons for CCMP, an intermediate of imidacloprid. CCMP can be synthesized through two different routes. The first is the route from 3-methylpyridine to 2-chloro-5-methylpyridine and then to CCMP. The second is the route from dicyclopentadiene to CCMP, a more economical and efficient one. Most of the imidacloprid production plants in China use the cyclopentadiene-acrolein process to produce CCMP. The process has a shorter route, costs less and has a better product quality. But it has high pollutant emissions, where every ton of imidacloprid consumes 14~28t of wastewater and generates 1.3~2.9t of waste residues and a large amount of acrolein, acrylonitrile and other toxic gases, which are difficult to treat and cause serious environmental pollution.

Since 2017, China gradually tightened its environmental protection policy, and some small factories with insufficient environmental protection technology and equipment were forced to shut down, decreasing utilization of production capacity of CCMP and imidacloprid, increasing concentration of the industry, and rising product prices.

3. 4-methylpyridine

Downstream derivatives of 4-methylpyridine

The downstream products manufactured with 4-methylpyridine derivatives as an intermediate are mostly high value-added products with excellent development prospects. Besides the well-known 2-chloro-4-trifluoromethyl pyridine obtained by chlorination and fluorination, which is used to produce aminopyralid and flonicamid, 2-amino-4-trifluoromethyl pyridine obtained by chlorination, fluorination and ammonia addition can be used to synthesize the active ingredients of anticancer drugs: MLN2480 and BKM120-AAA, of which the market price can reach several million yuan per ton. As the production of 2-amino-4-trifluoromethyl pyridine involves positioned catalytic chlorination, in-depth chlorination, fluorination and ammonization, and the synthesis is difficult, the product has high technical barriers.

On the whole, pesticide products are still the main direction of downstream development for methylpyridine. The biological activity of pyridine heterocyclic compounds after adding the fluoro is several times that of the original compounds, with less use rate and low residues in the soil, which meet the increasingly stringent environmental requirements. Therefore, the downstream fluorine-containing pyridine pesticides become the mainstay of the latest generation of pesticides. According to incomplete statistics, fluorine-containing compounds account for over 50% of the new pesticides developed in recent ten years.