Facile conversion of cis into trans oxane as liquid crystals.

Trans-oxanes are important liquid crystals. The commonly used techniques for the synthesis were to react 2-substituted propylene glycols with substituted formaldehydes. Such process produces toxic cis-oxanes, which are harmful to the environment. The cis to trans isomerization of wasted cis-oxanes was studied in the presence of p-toluenesulfonic acid as catalyst. The yield of cis to trans conversion was over 70%, which was much higher than 42-69% when traditional methods were employed. The total yield of the new method was increased to 90%. Further investigation of effects of catalysts, reaction times, temperatures on the cis-trans conversion was carried out. Proposed mechanism of this process for the conversion was discussed.


Results
The effect of the reaction conditions on the conversion. Reaction temperature. The effects of the reaction temperature on the cis to trans oxane conversion of mother liquors (f) were shown in Table 1. The temperatures of cis to trans isomerization of 2-p-cyanophenyl-5-ethyl-1,3-dioxane and 5-(4-n-propyl) cyclohexyl-2-p-ethylphenyl-1,3-dioxane were around 98 °C (n-heptane as solvent) to 110 °C (toluene as solvent). The corresponding trans isomers were obtained by recrystallization and the ratio of cis/trans conversion maintained at 25:75 as temperatures were increased.
The influence of reaction time. The influence of reaction time onthe cis to trans oxane conversion of mother liquors (f) was shown in Table 2. The cis-trans isomerization was completed in 1 h at 98 °C or 110 °C and there was no change of the cis-trans ratio when reaction time was increased. The proportion of cis-trans product remained at the level of 25:75 even though prolonged reaction time was applied.

Discussion
It was known that the conversion of the cis-trans isomer might be a chemical dynamic equilibrium process 13 , which was generally divided into three categories: photoisomerzation, thermoisomerization and catalytic isomerization. As the final cis-trans equilibrium was decided by the thermodynamic stability of each isomer, thermoisomerization and catalytic isomerization were classified into one group during the synthesis 14 . The isomerization was mainly focused on C=C, C=N 15 . The studies on the catalytic isomerization of cycloalkanes and heterocycles 16 were mainly concentrated on how to control cis-generation in ring-closure. However, the mechanism of how cis-isomers are converted into trans-ones is still unknown. It is also difficult to study the mechanism of catalytic isomerization because of the electronic and spatial effects of substituents on isomer molecules. Currently, only CNDO/2, SCF-MO and FSGO are used to roughly determine whether the mechanism of catalytic isomerization is based on the plane lateral displacement mechanism or the torsion mechanism under acid-base catalysis. We propose that the conversion process and the mechanism of the cis-trans isomerization of oxanes are as follows (Fig. 3): www.nature.com/scientificreports www.nature.com/scientificreports/ Oxanes undergo ring opening in the presence of p-toluenesulfonic acid to go through a planar intermediate state h, followed by the aldol condensation for ring closure to give cis (c) an d trans (d) acetal, respectively. The rearrangement process favors trans configuration as it is more stable thermodynamically. The experimental results showed the ratio of cis-trans compounds in the system was 25:75, and it was basically unchanged (Tables 1  and 2). This means experimental results supported the proposed mechanism.

Methods
Materials and equipments. SY 25000-type high-pressure liquid chromatograph (HPLC, methanol as mobile phase, C218 as the stationary phase, a flow rate of 1 mL·min-1); 1102 gas chromatograph (GC); HP 5989B mass spectrometer analyzer. p-cyanobenzaldehyde, toluene, calcium chloride and 2-ethyl propylene glycol were from Shanghai Reagent Factory (analytical grade). The anhydrous magnesium sulfate was also analytical grade from Tianjin Sitong Chemical Plant.
How to prepare the trans -2-p-cyanophenyl-5-ethyl-1,3-dioxane. The e1 prepared from above was recrystallized from ethanol at the ratio of 1 g/1.8 mL twice. The product was 34.6 g, and the purity of d1 was ≥99.5%, analyzed by gas chromatography (GC) and the purified yield was about 65%. The cis-trans mixture containing 2-p-cyanophenyl-5-ethyl-1,3-dioxane (f1) 17.4 g was obtained from the combined recrystallization mother liquor and the solvent was removed by distillation. Analysis of the sample by GC showed that the content of c1 was ≥58%, and d1 was ≥39%. f1 was directly used in following reaction.  www.nature.com/scientificreports www.nature.com/scientificreports/ Conversion of c1 to d1 under catalystic isomerization in the presence of p-toluenesulfonic acid. The cis-trans mixture (f1) 17.4 g (82 mM), p-toluenesulfonic acid 1.7 g (10 mM) and toluene 100 mL were successively added into 250 mL reaction flask equipped with mechanical stirrer, reflux condenser. The reaction mixture was heated under stirring. Analysis of the sample was carried out every 0.5 h and reflux continued for 3 h. When GC online results showed the cis-trans ratio remained unchanged, the reaction was quenched. The mixture was cooled and water 50 mL was added. The aqueous phase was extracted with toluene 20 mL. The organic phases were combined, washed with water to neutral, dried over anhydrous magnesium sulfate 5 g for 8 hrs and filtered. The filter cake was washed with toluene 10 mL twice. The cis-trans mixture (g1) 17.4 g was obtained after solvent removal and distillation.
Analysis of the sample by GC showed that c1 was ≥21%, and d1 was ≥78%. After recrystallization for purification, the product (d1) was 12.1 g with purity ≥99.5% analyzed by GC, and the yield was ≥69%. The mother liquor from recrystallization (f1) was collected and extracted. The overall yield of compound d1 based on p-cyanobenzaldehyde was ≥93% following the procedure of Fig. 2. conversion of cis-5-(4-n-propyl) cyclohexyl-2-p-ethylphenyl-1,3-dioxane (c6) to its corresponding trans configuration (d6) in the presence of p-toluenesulfonic acid. The cis-trans mixture (f6) 23 g containing 5-(4-propyl) cyclohexyl-2-p-ethylphenyl-1,3-dioxane was obtained following the same www.nature.com/scientificreports www.nature.com/scientificreports/ experimental procedure as above. Analysis of the sample by GC showed that c6 was ≥87% and d6 was ≥12%. In 250 mL reaction flask equipped with mechanical stirrer, reflux condenser and addition funnel, 23 g (73 mM) of cis-trans mixture of f6, 1.1 g (7 mM) of p-toluenesulfonic acid and 100 mL of n-heptane were added to the reaction flask. Then reaction mixture was heated under stirring. Analysis of the sample was carried out every 0.5 h and reflux continued for 3 hrs. When GC online results showed the cis-trans ratio was unchanged, the reaction was quenched. Then the reaction mixture was cooled and water 50 mL was added. The aqueous phase was extracted with n-heptane 20 mL. The organic phases were combined and washed with water to neutral, dried over anhydrous magnesium sulfate 5 g for 8 hrs and filtered, then washed with n-heptane 10 mL twice. The cis-trans mixture (g6) was obtained after distillation. Analysis of the sample by GC showed that cis-5-(4-n-propyl) cyclohexyl-2-p-ethylphenyl-1, 3-dioxane (c6) ≥23%, and trans-5-(4-n-propyl) cyclohexyl-2-p-ethylphenyl-1, 3-dioxane (d6) was ≥76%. After recrystallization and purification, the product (d6) was 14.8 g, the purity of d6 analyzed by GC was ≥99.5%, and the yield was ≥65%. The mother liquor from recrystallization was collected and extracted with the method described in Fig. 2. The overall yield of d6 was ≥70%.