purpose: synthesis of LIX 984N

LIX 984N is a 1:1 vol mixture of 2-hydroxy-5-nonylacetophenone ketoxime (LIX 84-I) and 5-nonylsalicylaldoxime (LIX 860-I)

1. Represents the chemical structure of LIX 84-I
2. Represents the chemical structure of LIX 860-I 

A- Preparation of oxime:

Classically, oximes are prepared [2] by refluxing an alcoholic solution of a carbonyl compound with hydroxylamine hydrochloride and pyridine. The method has multiple drawbacks such as low yields, long reaction time, toxicity of pyridine, and effluent pollution caused by the use of organic solvent.

However, 

Carbonyl compounds (aliphatic, heterocyclic, and aromatic) were converted into the corresponding oximes in excellent yields by simply grinding the reactants at room temperature without using any solvent in the presence of Bi₂O₃. Most importantly, this method minimizes waste disposal problems, provides a simple yet efficient example of unconventional methodology and requires short time.

Typical procedure for the formation of oxime 2

A mixture of aldehyde/ketone 1 (1 mmol), hydroxylamine hydrochloride (1.2 mmol), and Bi₂O₃ (0.6 mmol) was grounded in a mortar with a pestle for the required period of time. On completion of the reaction as monitored by TLC, ethyl acetate (2 × 10 mL) was added to the reaction mixture and filtered to separate the Bi₂O₃. The filtrate was concentrated down to approx. 6 mL, then added water to it when product precipitated out from the solution. The precipitate was filtered out and dried in high vacuum to furnish the pure oxime 2 in 60-98% yield.

B- substitution of the groups on benzene:

1- phenol preparation:

2- Friedel craft alkylation:

Synthesis process of 2-hydroxy-5-nonylacetophenone

embodiment 1:

In exsiccant 250ml round-bottomed flask, add 4-nonyl phenol 35.2g (0.16mol), 13g (0.32mol) anhydrous acetonitrile, 80ml anhydrous tetrahydro furan, the 4g Zinc Chloride Anhydrous feeds the exsiccant hydrogen chloride gas then, is warming up to 40 ℃ of about 4h of reaction, being cooled to 0 ℃ then and leaving standstill 3h, separate out the safran precipitation, promptly is the nonyl phenol ketoimine, filter, filter cake washs with tetrahydrofuran (THF), filter cake is changed in the there-necked flask of 1L, adds 0.6L hot water, backflow 1h, system becomes yellow solution, and cooling is filtered, filtrate is used decolorizing with activated carbon, product extracts with toluene, and underpressure distillation goes out solvent, gets product 2-hydroxyl-5-nonylacetophenone, yield 82%, purity 87%.

 embodiment 2:

In exsiccant 250ml round-bottomed flask, add 4-nonyl phenol 0.2mol, 0.3mol anhydrous acetonitrile, 100ml ether, the 6g aluminum chloride feeds the exsiccant hydrogen chloride gas then, is warming up to 30 ℃ of about 24h of reaction, being cooled to 10 ℃ then and leaving standstill, separate out the safran precipitation, promptly is the nonyl phenol ketoimine, filter, filter cake washs with ether, filter cake is changed in the there-necked flask of 1L, adds 0.7L hot water, backflow 1h, system becomes yellow solution, and cooling is filtered, filtrate is used decolorizing with activated carbon, product extracts with toluene, and underpressure distillation goes out solvent, gets product 2-hydroxyl-5-nonylacetophenone, yield 83%, purity 86%.

 embodiment 3:

In exsiccant 250ml round-bottomed flask, add 4-nonyl phenol 0.25mol, 0.32mol anhydrous acetonitrile, the mixed organic solvents of 120ml dry toluene and chlorobenzene, the mixture of 12g aluminum chloride and boron trichloride feeds the exsiccant hydrogen chloride gas then, be warming up to 100 ℃ of about 5h of reaction, being cooled to 5 ℃ then and leaving standstill, separate out the safran precipitation, promptly is the nonyl phenol ketoimine, filter, the filter cake toluene wash changes filter cake in the there-necked flask of 1L, adds 0.7L hot water, backflow 1h, system becomes yellow solution, and cooling is filtered, filtrate is used decolorizing with activated carbon, the product dichloromethane extraction, underpressure distillation goes out solvent, gets product 2-hydroxyl-5-nonylacetophenone, yield 84%, purity 87%.

Preparation of 5-nonylsalicylaldoxime

The formalin 200g of 220g4-nonyl phenol and 30% mass concentration is dropped in 1L four-hole boiling flask, adds 18g sodium carbonate, stir and be warming up to 70 DEG C, stratification after insulation reaction 2h, discard water layer, organic layer to be proceeded in 1L four-hole boiling flask and to add 200ml chloroform, add 178g Dess-Martin reagent (production of Wei Meng Chemical Co., Ltd. of Weifang City) again at 25 DEG C of reaction 2h, react complete and at room temperature use 200g saturated aqueous sodium carbonate successively, 200g sodium thiosulfate solution, stratification after 200g deionized water wash, discard water layer, organic layer is proceeded to 1L four-hole boiling flask, add the aqueous sodium carbonate 300g of 25% mass concentration, 30% mass concentration hydroxylamine sulfate solution 328g is instilled in 1h, dropwise at 60 DEG C of insulation reaction 3h, the aqueous sulfuric acid 60g adding 20% mass concentration neutralizes (pH is 6-7), stratification, get organic layer 200g deionized water and be washed till neutrality, finally distillation is except desolventizing, obtain finished product 5-nonyl salicyl aldooxime 261g, in 4-nonyl phenol, yield 99.24%, purity 98.30%.

In specific operation process, the sodium carbonate in a kind of or several replacement embodiment in sodium hydroxide, sodium bicarbonate, sodium methylate, triethylamine, pyridine also can be used to use.

Solvent extractant preparation

A- Synthesis process of 2-hydroxy-5-nonylacetophenone

Step 10: take the organic layer, proceed in a 4 holes boiling round bottom flask

Step 11: add the aqueous sodium carbonate

Step 12: add dropwise hydroxylamine sulfate solution (which occur for 1 hour).

Step 13: at a 60 degrees for 3 hours reaction, add dropwise the aqueous sulfuric acid (neutralization of ph)

Step 14: stratification

Step 15: wash the organic layer with ionized water.

Step 16: distillation