Alkylation Of 3-Hydroxy Of L-ascorbic Acid

L-ascorbic acid has a very important role in daily life,but when it comes to light or heat conditions,it is unstable.so we need to modify L-ascorbic acid to increase the stability of ascorbic acid.The modification of the hydroxyl group at the 3-position is the simplest and the product stability is best.However,when the 3-position hydroxyl group is modified,it is easy to get product that the 2,3 hydroxyl groups are protected.What'more,the reaction of the raw material is incomplete.In this paper,we mainly to do the following aspects:First,the methods of alkylation of 3-hydroxy of L-ascorbic acid are mainly three-step and one-step method in currently.The one-step method mainly uses the two-phase phase transfer catalyst to directly alkylate the 3-hydroxyl of L-ascorbic acid and the alkylation of L-ascorbic acid at the 3-position hydroxyl group by microwave reactor.The three-step method mainly uses NaHCO₃?CsF and the like,but,the above-mentioned methods have their own disadvantages.Depending on the complexity of the structure,the simplicity of the reaction steps and the environmental protection,there is still a need to develop new methods.In the early stage,we used bromobenzyl as the alkylating reagent to explore the one-step reaction and the three-step reaction.In one step method when using water and ethanol as solvent,sodium hydroxide to do the reaction,yield was 45%.However,the scope of application of this has narrow range and is not suitable for popularization.In the three-step exploration,we optimized a series of bases and solvents and found that when using 0.5 equivalents of sodium methoxide and 1 equivalent of triethylamine and acetonitrile as solvent.The yield of 5,6-isopropylidene-3-O-benzyl-L-ascorbic acid was up to 46%.Second,in order to improve the purity of the product,increase the utilization of L-ascorbic acid,we developed a recycling method.The yield of monoalkylation is from51%to 80%.In the case of bromoethane,the utilization of 5,6-isopropylidene L-ascorbic acid increased from 40%to 51%after 4 cycles.Thirdly,We used 3-O-benzyl-L-ascorbic acid and 5,6-isopropylidene-3-O-benzyl-L-ascorbic acid as a starting material to investigate 2-O-?-D-glucopyranosyl-L-ascorbic acid.We found that the use of 5,6-isopropylidene-3-O-benzyl-L-ascorbic acid and bromoetetraacetylated glucose in the two-phase phase transfer catalyzed reaction of fully protected 2-O-?-D-glucopyranosyl-L-ascorbic acid in a yield of 48%.And then we optimize the removal of the fully protected product.We found that firstly acid 5,6-bit ring,and then deacetyl,and finally debenzylation is better than first off the benzyl,and then open the 5,6-bit ring,and finally deacetyl.Yield can be improved 47%.