In-situ generated ionic liquid catalyzed aldol condensation of trioxane with ester in mild homogeneous system

α, β-unsaturated esters were often synthesized from aldehydes and esters in the presence of strong organic base that was very sensitive to air and moisture via aldol reaction. Trioxane was very useful C1 resource, however, the decomposition of it was always the challenging problem that facing researchers. Herein, a novel synthetic methodology for α, β-unsaturated ester preparation from trioxane and ester with mild catalysis of generated ammonium trifluoromethanesulfonate ionic liquid. The enolization of ester as well as the decomposition of trioxane could proceed easily in the presence of boryl trifluoromethanesulfonate and amine at 20–25℃. Then the enolate and decomposed formaldehyde occurs aldol reaction to form α, β-unsaturated ester. With this strategy, the yield and selectivity of product from various substrates including aliphatic esters,lactones and thioester could reach up to 85.2% and 90.1%.

Bronsted-acidic ionic liquids as catalysts for synthesizing trioxane

The batch reaction experiments have been made for the first time to investigate the effect of ionic structure on the reactivity and selectivity of the trioxane-forming reaction catalyzed by a Br?nsted-acidic ionic liquid(IL).The ILs considered include 1-cyclohexyl-2-pyrrolidinonium trifluoromethanesulfonate([NCy P][TfO ]),1-cyclohexyl-2-pyrrolidinonium benzenesulfonate([NCyP ][BSA]),1-cyclohexyl-2-pyrrolidinonium p-toluenesulfonate([NCyP ][pTSA]),1-octyl-2-pyrrolidinonium 2,4-dinitrobenzenesulfonate([NOP][DNBSA]),1-octyl-2-pyrrolidinonium benzenesulfonate([NOP][BSA]),1-octyl-2-pyrrolidinonium methanesulfonate([NOP][MSA]),and 1-octyl-2-pyrrolidinonium trifluoromethanesulfonate([NOP][Tf O]).It is found that the yield of trioxane in the reaction solution correlates inversely with the Hammett acidity function H0 of the aqueous solution of the corresponding ILs.Variation of the cation structure from [NCyP ]+to [NOP]+exerts little influence on the yield and the selectivity of trioxane in the reaction solution.Using [TfO ]-or [DNBSA]-in place of [MSA]-or [BSA]-apparently increases the yield of trioxane,but only slightly increases the concentration of formic acid in the reaction solution.The continuous production experiments have been made to investigate the performance of [NOP][MSA],[NOP][DNBSA],[NCyP ][TfO ],and H2SO4 as an extraction distillation agent.Such effect of [NCyP ][TfO ] considerably overrides that of H2SO4.The yield and the selectivity of trioxane are both increased when [NCyP ][TfO ] is used instead of H2SO4 at a reaction time 5 h.

ReCl（CO）5-catalyzed Reactions of Aromatic Compounds with 1,3,5-Trioxane or Aqueous Formaldehyde Affording Diarylmethanes

ReCI（CO）5 catalyzed the dehydration reaction of aromatic compounds with 1,3,5-trioxane or aqueous formaldehyde （37 wt%） under air. The reactions of a variety of aromatic compounds beating electron-donating group（s） with 1,3,5-trioxane afforded the corresponding diarylmethanes in moderate to good yields.

Assay method for quality control and stability studies of a new antimalarial agent (CDRI 99/411)

CDRI compound no. 99/411 is a potent 1,2,4-trioxane antimalarial candidate drug under development at our Institute. An HPLC method for determination of CDRI 99/411 with its starting material and intermediates has been developed and validated for in process quality control and stability studies. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection （LOD） and lower limit of quantification （LLOQ） were determined according to International Conference on Harmonization ICH Q2（R1） guidelines. HPLC separation was achieved on a RP-select B Lichrosphere~ column （250 mm x 4 ram, 5 lam, Merck） using water containing 0.1% glacial acetic acid and acetonitrile as the mobile phase in a gradient elution. The eluents were monitored by a photo diode array detector at 245 and 275 nm. Based on signal to noise ratio of 3 and 10 the LOD of CDRI 99/411 was 0.55 μg/mL, while the LLOQ was 1.05 μg/mL. The calibration curves were linear in the range of 1.05- 68 μg/mL. Precision of the method was determined by inter- and intra-assay variations within the acceptable range.

Efficient synthesis of poly(oxymethylene) dimethyl ethers over PVP-stabilized heteropolyacids through self-assembly

A series of polyvinylpyrrolidone-stabilized heteropolyacids(PVP-HPAs)are generated by self-assembly of HPAs and PVP in methanol.The PVP-HPAs are then employed as catalysts for the synthesis of poly(oxymethylene)dimethyl ethers(DMMn,n1)by the methanolysis of trioxane.The results suggest that the acidity of PVP-HPAs is tunable by changing the ratio of PVP and HPAs,which is a key factor for the selectivity of the DMMn product.By optimizing the composition and reaction conditions,two types of PVP-HPA,PVP-phosphotungstic acid(PVP-HPW)in a PVP/HPW ratio of 1/4:1 and PVP-silicotungstic acid(PVP-HSi W)in a PVP/HSi W ratio of 1/4:3/4,respectively afford 52.4%and 50.3%yields of DMM2–5.The optimized catalysts are reusable for a minimum of 10 times without a significant drop in performance.