At present, the synthetic methods of Sodium Laureth Sulfoacetate mainly include the following three categories:
The first type of method: the mixture of calcium laurate and calcium acetate is obtained by the reaction of lauric acid, glacial acetic acid and slaked lime, and then the calcium salt mixture is reacted under high temperature conditions to obtain dodecyl ketone, which is then condensed with ethyl formate to obtain dodecyl ketone. Acetaldehyde, and then added with sodium bisulfite to obtain Sodium Laureth Sulfoacetate.
In the process of preparing dodecaketone by the synthetic method, the temperature requirements are relatively high, the conditions are harsh, and the production cost is high, which is not conducive to large-scale industrial production.
The second type of method: using 1-bromo-n-decane and ethyl acetoacetate as raw materials, alkylation and decarboxylation to obtain 2-tridecone, and condensation with ethyl formate through ester ketone to obtain dodecanoylacetaldehyde, and finally Addition of dodecanoylacetaldehyde and sodium bisulfite to obtain Sodium Laureth Sulfoacetate.
The synthesis method is found in “Qilu Pharmaceutical Affairs” 2006.8, Synthesis of Sodium Laureth Sulfoacetate . The synthetic route is complicated, the total yield is not high, and it is only suitable for laboratory preparation.
The third type of method: use methylundecanone as raw material to react with metal sodium and toluene as solvent, extract sodium dodecanoylacetaldehyde from toluene with distilled water, and finally combine sodium dodecanoylacetaldehyde with sulfurous acid Sodium hydrogen is added in a weakly acidic environment to obtain sodium a-hydroxydodecanoylethylsulfonate, namely Sodium Laureth Sulfoacetate .
The synthesis method refers to the three-step synthesis method of the synthesis process of Houttuyniacin sodium, which is found in “Anhui Medicine” 2004.2 New Synthesis Research of Sodium Laureth Sulfoacetate . This process has harsh production conditions and high cost, and is not suitable for large-scale production.
(1) get coconut oil 3500g, put in an enamel container, add sodium hydroxide 750g and sulfuric acid 250g respectively, after saponification and acidification; Put in the vacuum fractionation device, at 150 DEG C, under the condition of pressure 120mmHg, vacuum fractionation, Preparation of dodecanoic acid;
(2) Preparation of calcium salt
Take 1800g of sieved lime and add 2500ml of water and stir it into a paste, and heat 500g of dodecanoic acid in a 10,000ml porcelain bucket to dissolve it completely, mix it with 2500g of glacial acetic acid, pour it into the lime paste, and keep stirring to form calcium salt , placed overnight (to make calcium salt);
(3) Mixed ketone preparation:
The obtained calcium salt was put into a cracking tank, and heated under direct fire for 10 hours to crack to obtain about 750ml of mixed ketones;
(4) Preparation of tridecone-2 (fractionation)
Take 1000ml of mixed ketone, pour it into a round-bottomed flask, add 2 to 3 glass beads to prevent waterfall boiling, connect a fractionation device, and then heat (the temperature is controlled at 150°C and the pressure is controlled at 120mmHg) under reduced pressure distillation. The fractions within the range are weighed to obtain tridecone-2;
(5) preparation of dodecanoylacetaldehyde sodium salt:
Take 200 g of tridecone-2, 750 g of ethyl formate, and 1000 ml of anhydrous benzene, mix them in a 5000 ml conical flask, and then take 125 g of sodium metal, chop them, put them into the mixed solution in stages, and shake them thoroughly. The conical flask is for external use. Cooling with ice water, keeping the reaction solution at 25°C and leaving it at room temperature, to obtain sodium dodecanoylacetaldehyde;
(6) Addition of sodium dodecanoylacetaldehyde sodium bisulfite
Take the above reactant and extract it with water 4 times: 2000ml×2, 1000ml×2, combine the 4 water extracts, take another 750g NaHSO3 dissolve in 1500ml water, mix with 250ml glacial acetic acid, add the above water extract, and immediately generate a lot of white precipitates, Stir well, place the liquid, filter, filter dry, place the liquid, pour the precipitate into a porcelain bucket, heat and boil in a water bath with 50% ethanol 8000ml, filter, heat and boil the filtrate in a water bath and place overnight for reconstitution. After crystallization, suction-filtered to dryness, washed with about 1500ml of ether in different times, then washed with water, washed with ether until white, drained, and dried at 80°C to obtain new houttuyniacin sodium.