Role of Calcination Temperature on Isosorbide Production from Sorbitol Dehydration over the Catalyst Derived from Ce(IV)Sulfate

Isosorbide is a multi-purpose chemical that can be produced from renewable resources.Specifically,it has been investigated as a replacement for toxic bisphenol A(BPA)in the production of polycarbonate(PC).In this study,the synthesis of isosorbide by sorbitol dehydration using a cerium-based catalyst derived from calcined cerium(IV)sulfate(300°C,400°C,450°C,500°C,and 650°C)was investigated.The reaction occurred in a high-pressure reactor containing nitrogen gas.Advanced instrumental techniques were applied to analyze the characteristics of the calcined catalyst.The results showed that the calcined catalysts demonstrated different crystalline structures and sulfate species at different temperatures.However,the acidic properties(strength and amount)of the catalyst did not change with the calcination temperature.The cerium(IV)sulfate calcined at 400°C exhibited the best catalytic performance,achieving the highest isosorbide yield(55.7%)and complete conversion of sorbitol at 180°C,20 bar of N2,and 6 h using CeSO-400.The presence of a sulfate group on the catalyst was the most important factor in determining the catalytic performance of sorbitol dehydration to isosorbide.This work suggests that CeSO-400 catalysts may play an important role in reducing reaction conditions.

A continued study on the bisoprolol and isosorbide dinitrate transdermal patches:cardiovascular protection in spontaneously hypertensive rats

The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.

Synthesis of isosorbide-based polycarbonates via melt polycondensation catalyzed by quaternary ammonium ionic liquids

A series of quaternary ammonium ionic liquids(ILs)were synthesized and employed as catalysts for the production of poly(isosorbide carbonate)(PIC)from diphenyl carbonate and isosorbide via a melt polycondensation process.The relationship between the anions of the ILs and the catalytic activities was investigated,and the readily‐prepared IL tetraethylammonium imidazolate(TEAI)was found to exhibit the highest catalytic activity.After optimizing the reaction conditions,a PIC with a weight‐average molecular weight(Mw)of25600g/mol was obtained,in conjunction with an isosorbide conversion of92%.As a means of modifying the molecular flexibility and thermal properties of the PIC,poly(aliphatic diol‐co‐isosorbide carbonate)s(PAIC)s were successfully synthesized,again using TEAI,and polymers with Mw values ranging from29000to112000g/mol were obtained.13C NMR analyses determined that the PAIC specimens had random microstructures,while differential scanning calorimetry demonstrated that each of the PAICs were amorphous and had glass transition temperatures ranging from50to115°C.Thermogravimetric analyses found Td‐5%values ranging from316to332°C for these polymers.Based on these data,it is evident that the incorporation of linear or cyclohexane‐based diol repeating units changed the thermal properties of the PIC.

Asymmetric synthesis of 3-butylphthalide using isomannide and isosorbide as chiral auxiliaries

A new approach for asymmetric syntheses of （S） and （R）-3-n-butylphthalide （NBP） is presented. The diastereoselective addition of dibutylzinic to aromatic aldehyde 10 or 11 generated from isomannide- or isosorbide-derived chiral auxiliary afforded S-NBP or R-NBP in high optical yields.

Halogen-Free Flame Retarded Poly(Lactic Acid)with an Isosorbide-Derived Polyphosphonate

Fabrication of flame retardants from renewable biomass has aroused extensive interest over the past decade.This work reported a synthesis of isosorbide-derived polyphosphonate(PICPP)as an anti-flammable agent for poly(lactic acid)(PLA).The presence of PICPP notably declined the storage modulus of PLA/PICPP owing to the declined molecular weight of PLA catalyzed by the presence of PICPP.PLA and PLA/PICPP thermally degraded in one stage under either air or nitrogen atmosphere.With increasing the amount of PICPP,the onset thermal decomposition temperature of PLA/PICPP was decreased gradually,owing to the earlier decomposition of PICPP.With only 10 wt%of PICPP,PLA/PICPP-10 achieved a high limiting oxygen index of 30.0%and UL-94 V-0 classification,manifesting that PICPP was an efficient anti-flammable agent for PLA.The inclusion of 15 wt%PICPP also caused 33%and 16%decline in PHRR and THR of PLA,respectively.TG-IR results clarified that PLA/PICPP produced the less typical pyrolysis products especially flammable carbonyls than PLA,which may account for the suppressed PHRR and THR values of PLA/PICPP.

Quantitative Evaluation of the Antiischemic Effect of Isosorbide Dinitrate

Objectives To evaluate the anti- ischemic effect of ISDN on the patients with coronary heart disease . The change in the size of the defect area as percentage of the entire myocardium as determined by the unfolded surface mapping between the baseline and after ISDN infusion reflects the anti-ischemic effect of ISDN. Methods and Results 99m Tc-MIBI myocardial perfusion SPECT images were acquired, and reconstruction of the bull's eye map and unfolded surface mapping were performed according to the dates of tomography images. In the group (99mTc-MIBI was injected at 30 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was 33.01 ± 5.35% at baseline, (28.9 ±5.23)% after ISDN was infused (P < 0.05); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (22.06±5.58)% at baseline, (19.60±4.07)% after ISDN was infused (P < 0.05); the sum of defect blood ST segments is 60 at baseline, 51 after ISDN was infused. In the group (99mTc-MIBI was injected at 60 minutes after the start of ISDN iv drip): at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (29.20±5.08)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (21.2 ± 5.49)% at baseline, (17.52±5.59)% after ISDN was infused (P < 0.001); the sum of defect blood ST segments is 58 at baseline, 47 after ISDN was infused. In the group (99mTc-MIBI was injected at 150 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (32.87 ±6.46)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (18.42± 5.17)% at baseline, (14.18±3.61)% after ISDN was infused (P< 0.001); the sum of defect blood ST segments was 64 at baseline, 41 after ISDN was infused. Conclusions The unfolded surface mapping of 99mTc- MIBI myocardial perfusion image can be used as a method of quantitatively evaluating the anti-ischemic effect of drugs and ISDN iv drip can improve the blood flow in myocardium (myocardium perfusion).

Studies on the Diastereoselective Alkylation Reaction Employing Isomannide and Isosorbide as Chiral Auxiliaries

The studies on the asymmetric alkylation of ester employing D-Isomannide and D-isosorbide as chiral auxiliaries were described. The diastereomeric excess of this reaction was up to 90%.

Experiments and kinetic modeling of the sorbitol dehydration to isosorbide catalyzed by sulfuric acid under conditions of non-constant volume

Isosorbide is a novel bio-based material derived as a secondary dehydration product of sorbitol.This work focuses on the kinetics of sulfuric acid-catalyzed dehydration of sorbitol under conditions of nonconstant volume.Herein,the effects of stirring rate,catalyst dosage,reaction temperature,and reaction time on the dehydration reaction of sorbitol were investigated.The yield of isosorbide up to 77.13%was obtained after 1.5 h of reaction time under conditions of 2 kPa,1.0%(mass)catalyst dosage,and 413.15 K.Based on the sorbitol dehydration reaction mechanism and a simplified reaction network,a kinetic model was developed in this work.A good agreement was accomplished between kinetic modeling and experiments between 393.15 and 423.15 K.The fitting results indicate that side reactions with higher activation energies are more affected by reaction temperatures,and the main side reaction that influences the selectivity of isosorbide is the oligomerization reaction among the primary dehydration products of sorbitol.The model fitting of the catalyst amounts effect shows that the effective concentration of sulfuric acid would be reduced with the increase of dosage due to the molecular agglomeration effect.Hopefully,the kinetic experiments and modeling results obtained in this work will be helpful to the design and optimization of the industrial sorbitol dehydration process.

Studies on Isosorbide-enhanced Biodegradable Poly(ethylene succinate)

To improve the mechanical properties of bio-based poly(ethylene succinate),the sugar monomer isosorbide,whicli is relatively easy to obtain,was used as a copolymerized third monomer to synthesize poly(ethyleneco-isosorbide succinate),a 100%biomass copolyester.The effects of isosorbide on the crystallinity and thermal properties of copolyester were studied by nuclear magnetic resonancefH NMR),differential scanning calorimeter(DSC),and thermogravimetric(TG).Owing to its distinct rigid bicyclic structure,isosorbide can improve the glass transition temperature of the copolyester and decrease the crystallization rate,as well as accelerate the hydrolysis of the copolyester.Simultaneously,the introduction of isosorbide can effectively improve the antistatic properties of copolyester.

Synthesis of Poly(isosorbide carbonate) via Melt Polycondensation Catalyzed by a KF/MgO Catalyst

MgO loaded with KF was prepared by using tlie impregnation method and was employed as the catalyst for tlie direct traiisesterification of diphenyl carbonate(DPC) witli isosorbide to synthesize high-molecular-weight poly(isosorbide carbonate)(PIC). The relationship between physical-chemical properties and catalytic performance for KF/MgO in this melt process was investigated by various characterization techniques. The basic site amount and strength were found to be responsible for this transesterification process, and the medium and strong basic sites tended to promote the polycondensation reaction. 20-KF/Mg0-500 exhibited the best catalytic performance, giving PIC with Mw of 84200 and glass transition temperature(rg) of 173℃ under optimal conditions. Additionally, 20-KF/MgO-500 was found to catalyze the transerification of DPC with isosorbide and other diols to syntliesize the corresponding poly(aliphatic diol-co-isosorbide carbonate)s(PAICs). This excellent activity can be ascribed to the presence of an abundance of basic sites and their specific basic strength on the surface of KF/MgO.

Synthesis of Poly(isosorbide carbonate) via Melt Polycondensation Catalyzed by Ca/SBA-15 Solid Base

Ca/SBA-15 solid bases with different Ca/Si atomic ratios were prepared by a one-pot route and employed as catalysts for the production of poly（isosorbide carbonate） （PIC） from diphenyl carbonate and isosorbide via a transesterification polymerization process. The relationship between physicochemical properties and catalytic performance for Ca/SBA-15 in this melt process was investigated by means of various characterization techniques. It was found that basic site amount and strength were responsible for this transesterification process; the weak and medium basic sites inclined to promote polycondensation reaction. It was worth noting that strong basic sites could favor the decomposition of the resultant P/C, resulting in the decrease of weight-average molecular weight （Mw） and yield, and the sample with Ca/Si atomic ratio of 0.4 exhibited the best catalytic performance, giving PIC with Mw of 4.88 × 10^4 g/mol and Tg of 169 ℃ at the optimal conditions. This excellent activity can be ascribed to the presence of rich basic sites and specific basic strength on the surface of 0.4Ca/SBA-15.

Insights into the Active Acid Sites for Isosorbide Synthesis from Renewable Sorbitol and Cellulose on Solid Acid Catalysts

Sustainable synthesis of isosorbide, an important renewable platform chemical, from sorbitol and cellulose, has attracted increasing attention, but still remains challenging. Here, we have studied the effects of the acidity on the dehydration of sorbitol in water on a variety of solid acids, including zeolites, sulfonic materials, montmorillonite and mixed SiO2-Al2O3 oxide. These solid acids showed markedly different activities, which were found to be closely related to their strong Brønsted acid sites, while the weak Brønsted acid and Lewis acid sites were essentially inactive. Different from the other solid acids examined, H-ZSM-5 zeolites in a wide range of Si/Al molar ratios(25-300) exhibited superior selectivities to isosorbide in dehydration of sorbitol, consistent with the observed difference in their formation rates of the 1,4-sortbitan and 3,6-sorbitan intermediates. Kinetic studies on the sorbitol dehydration showed that 3,6-sorbitan, once it formed, dehydrated to isosorbide more readily than 1,4-sorbitan by a factor of 19, and the formation rate constant of 3,6-sorbitan on H-ZSM-5(Si/Al=25) was about three times higher than that of H-Beta(Si/Al=25). Such favorable formation of the reactive 3,6-sorbitan intermediate and the higher isosorbide selectivity on H-ZSM-5 appear to be induced by its confined pore structure composed of the paired 5-membered rings. H-ZSM-5 was also found to be efficient for the direct conversion of cellulose to isosorbide in coupling with Ru/C hydrogenation catalyst. This work provides fundamental insights into the acidity and pore structures that are helpful for the design of novel solid acids toward the efficient synthesis of isosorbide from the dehydration of sorbitol and even directly from the tandem reaction of cellulose.

Synthesis of renewable isosorbide-based monomer and preparation of the corresponding thermosets

Two kinds of difunctionalized isosorbide derivatives containing norbornene groups were designed and synthesized by a facile one-step reaction under mild conditions.~1H NMR spectroscopy confirmed the chemical composition and differential scanning calorimetry（DSC） revealed the distinct curing behaviors between conventional petroleum-based dicyclopentadiene（DCPD） and synthesized renewable isosorbided-based monomer（ISN）. In contrast to DCPD, ISN was low viscous liquid at room temperature and had even higher reactivity to perform ring-opening metathesis polymerization（ROMP） in the presence of Grubbs＇ catalyst. Due to the presence of flexible and elastic Si–C long chains, the cured poly（ISN） thermosets not only had good mechanical properties but also exhibited much higher storage modulus at the rubbery state in comparison with traditional poly（DCPD）.

Samarium diiodide induced asymmetric synthesis of γ-butyrolactone using chiral auxiliaries derived from isosorbide and isomannide

The asymmetric reductive coupling reaction of various acrylates derived from D-isosorbide and D-isomannide with acetophenone mediated by samarium diiodide to give both enantiomers of the optically active γ-butyrolactone was described. The best enantiomeric excess of the products was 60%.

Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility

AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.

Pre-Induction Cervical Ripening Using a Transcervical Foley Catheter Combined with ISMN Vaginal Tablets for Vaginal Birth after Previous Caesarean Section (VBAC)—A Comparative Study

Objective: To compare the effectiveness, safety and client acceptability of concurrent application of transcervical Foley catheter with vaginal ISMN-sustained release (SR) 60 mg tablet versus transcervical Foley catheter alone for pre-induction cervical ripening in women who are undergoing Vaginal birth after C-section (VBAC). Method: A prospective single blind randomized control study was carried out including 110 pregnant women who had unfavorable cervix (MBS less than 6) at 40 weeks and 3 days of gestation. The two groups received either the trans-cervical foley catheter with a vaginal ISMN 60 mg sustained release (SR) tablet on 40 weeks and 3 days (Treatment arm 1, n = 57), or trans-cervical Foley alone on 40 weeks and 3 days (Treatment arm 2, n = 53). Results: At 40 weeks + 3 days gestation, the mean age, mean parity and the mean modified Bishop Score (MBS) were comparable among the two treatment groups. Majority (n = 98, 89.1%) remained without spontaneously establishing labour at 24 hours of intervention. The difference in mean MBS at 40 weeks + 4 days (24-hours following the intervention) in the two groups was statistically not significant (P > 0.05). The group who received concurrent ISMN vaginal tablets achieved a higher number of successful VBACs (n = 33, 62.3%) over the group who received the Foley catheter only method (n = 29, 50.9%), however, not statistically significant (P > 0.05). Conclusions: The concurrent use of vaginal ISMN tablets (60 mg SR) with a transcervical Foley catheter failed to show higher effectiveness compared to a transcervical Foley catheter alone as an induction method.

Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter

AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical fi eld stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10-7-10-4 mol/L) and SNP (10-8-10-4 mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 x 10-4 mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and Emax obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.

A Clinical Investigation on Tong Xin Luo Capsule in Treatment of Coronary Heart Disease with Silent Myocardial Ischemia

36 cases of coronary heart disease with silent myocardial ischemia (SMI) were treated sequentially with Tong Xin Luo (TXL) capsule and isosorbide dinitrate in random order. The results showed that both drugs were effective in decreasing episodes of SMI and shortening the duration of asymptomatic myocardial ischemia. TXL, however, was found with a better action and was superior to isosorbide dinitrate. It was also found that TXL could improve diastolic function of the left ventricle as well.

Rational design of sustainable polyurethanes from castor oil: towards simultaneous reinforcement and toughening

Sustainable polyurethanes prepared from castor oil and diisocyanates show very low strength and toughness, due to the highly cross-linked and flexible structure. Herein, we report a new strategy to simultaneously reinforce and toughen castor oil-based polyurethane via incorporating a stiff component （isosorbide, IS） to enhance network stiffness and reduce crosslink density. The crosslinking degree de- creases while the strength, moduli, ductility and heat re- sistance significantly increase accordingly with increasing IS content. The tensile behaviors are tunable over a broad range （either as elastomers or as plastics） depending on the com- positions. The polyurethanes show excellent thermal stability with onset decomposition temperature higher than 280℃. The investigation provides a new hint for future design and fab- rication of high performance sustainable polymers from other vegetable oils.