Studies on 4-thiazolidinones. I. Cleavage of 3-Phenyl-2,4-thiazolidinediones with benzylamine and hydrazine

5-Arylidene-3-phenyl-2,4-thiazolidinediones 1a – h undergo ring cleavage with excess benzylamine to give an equimolar mixture of phenyl benzyl urea 5 and dibenzyl urea 6 . The intermediate in this type of reaction is isolated under controlled conditions and proved to be 1,5-dibenzyl-3-phenyl biuret 3 . Using hydrazine, each of 1d – g gives the corresponding biuret derivative 7a – d , respectively. The cleavage occurs at 1,2 as well as 4,5 bonds.     

4-氨基-3-异丙基-5-氧-1H-l,2,4-三唑的合成工艺研究

研究了胺唑草酮重要中间体4-氨基-3-异丙基-5-氧-1-H-l,2,4-三唑(MNHN)的合成工艺,优化的工艺条件为:反应温度90℃,反应时间4 h,n(MNHO)∶n(水合肼)∶n(氢氧化钠)=1∶1.1∶0.3。此条件下得到产品纯度为97.0%,收率达92.0%。     

2，4－二氯－5－氟苯乙酮生产工艺研究

本文对２，４－二氯－５－氟苯乙酮的生产工艺进行了研究和探讨。将研究结果应用于工业生产，取得了良好的经济效益。     

4-甲基-3-癸烯-5-醇的合成工艺研究

目的：改进4-甲基-3-癸烯-5-醇的反应条件及工艺路线,提高收率,使其更有利于工业化生产。方法：以正丙醛为原料,在碱性下缩合,得到2-甲基-2-戊烯醛;再以正戊醇为原料,与二氯亚砜反应得到1-氯代戊烷,然后再和镁反应制得格氏试剂正戊基氯化镁;再将2-甲基-2-戊烯醛和正戊基氯化镁反应,经过亲核取代、消除反应后,即得4-甲基-3-癸烯-5-醇。结论：所得产物经过理化性质鉴别以及结构确证,可以进一步证明与目标化合物一致,产品经GC分析,含量达98．0％以上。     

4-氨基-3-异丙基-5-氧-1H-1,2,4-三唑的合成工艺研究

研究了胺唑草酮重要中间体4-氨基-3-异丙基-5-氧-1-H-1,2,4-三唑(MNHN)的合成工艺,优化的工艺条件为:反应温度90℃,反应时间4h,n(MNHO):n(水合肼):n(氢氧化钠)=1:1.1:0.3.此条件下得到产品纯度为97.0％,收率达92.0％.     

基于Ugi-4CC反应合成2,4-二取代-5-氨基噻唑衍生物

采用基于Ugi-4CC(four-component coupling)反应5-氨基噻唑的合成方法合成了9个2,4-二取代5-氨基噻唑,所有化合物的结构均经~1H NMR、13C NMR及IR确证,部分化合物的结构经IR确证;实现了重结晶法提纯目标化合物,相比文献柱层析法,提高了合成效率,降低了合成成本,研究结果使该方法更具实用性和通用性。     

3-氟-4-硝基苯酚的合成研究

研究了以2,4-二氟硝基苯为原料,经甲氧基化、脱甲基化反应合成3-氟-4-硝基苯酚的新方法。探讨了反应条件对反应的影响：甲醇钠与2,4-二氟硝基苯物质的量比1：1,回流反应4h,得单氟代硝基苯甲醚;AlCl3与氟代硝基苯甲醚按物质的量比2．5：1在苯中回流反应10h,再经水蒸汽蒸馏分离提纯制得3-氟-4-硝基苯酚,质量分数99．5％,总收率38．7％。通过熔点测定、红外光谱和核磁共振等对产物结构进行了表征。     

3-(2-氟-4-氯-5-甲氧羰基乙巯基苯基)-5-异丙叉基恶唑烷-2,4-二酮的合成

通过2-氟-4氯-5甲氧羰基乙巯基苯基异氰酸酯与2—羟基—3—甲基—3—丁烯酸乙酯发生加成、闭环反应制得除草剂3—(2—氟-4氯—5—甲氧羰基乙巯基苯基)—5-异丙叉基噁唑烷—2，4-二酮，优化反应条件为n(异氰酸酯)：n(2—羟基—3—甲基—3—丁烯酸乙酯)＝1：1．25—1：1．30。     

Studies on melt spinning. VIII. The effects of molecular structure and cooling conditions on the severity of draw resonance

The effects of molecular structure and cooling conditions on the severity of draw resonance was investigated by carrying out carefully controlled melt spinning experiments. For the study, two types of polymeric materials were used: one which exhibits viscoelastic behavior (high-density polyethylene, polypropylene, and polystyrene), and the other which exhibits almost Newtonian behavior [nylon-6 and poly(ethylene terephthalate)]. In order to investigate the effect of cooling on the severity of draw resonance, different methods of cooling the molten threadline were employed. In one set of experiments, isothermal chambers of various lengths (3, 6, and 12 in.) were attached to the spinnerette face, so that the molten threadline, upon exiting from the spinnerette, began to cool in the ambient air only after it had passed through the isothermal chamber. This method of cooling is called “delayed cooling,” providing both an isothermal region (inside the isothermal chamber) where only stretching occurs, and a nonisothermal region (outside the isothermal chamber) where both stretching and cooling occur simultaneously. In other experiments, the temperature profile of the molten threadline was controlled by adjusting the temperature of the heated chamber. This method of cooling provides a gradual drop of the threadline temperature, compared to the more sudden drop when spinning into a cold environment provided at the spinnerette exit. The severity of draw resonance was recorded on movie film, and the thread tension was measured with a low-force load cell transducer and recorded on a chart recorder. The temperature of the threadline along the spin direction was measured using a fiber optical probe attached to a Vanzetti Infrared Thermal Monitoring System (Model TM-1). It was found that the severity of draw resonance depended on the molecular structure and the way the molten threadline was cooled. Of particular interest is the observation that, for the viscoelastic materials investigated, cooling destabilized the molten threadline outside the isothermal chamber. This gave rise to more severe resonant behavior, at and above the critical draw-down ratio, in contradiction to the theoretical prediction by Fisher and Denn. It was observed, also, that the elasticity of the materials tended to destabilize the molten threadline (i.e., it increased the severity of draw resonance), again in contradiction to the theoretical prediction of Fisher and Denn. It is believed that morphological changes of polymers may play an important role in the occurrence of draw resonance when a melt threadline is stretched under cooling. Our study indicated that a good understanding of draw resonance of viscoelastic fluids requires more careful study than the classical hydrodynamic stability analysis reported by Fisher and Denn. They based their analysis on several convenient and yet unjustified assumptions, and solely on phenomenological considerations. We suggest that future theoretical analysis of draw resonance be carried out by considering a fluid model with a nonlinear memory function in order to properly account for the deformation history of the fluid, and the relaxation and cooling processes in the die swell region and the region below it.     

3－氯－4－氟硝基苯气相氯化反应动力学

研究了由３－氯－４－氟硝基苯气相氯化合成２．４－二氯氟苯的影响因素。在５５８～６５９Ｋ温度范围内测定动力学数据，根据实验数据得到反应速率方程式为ｋ＝１．２４４×１０５ｅｘｐ（－６２８５／Ｔ）     

The role of the 11-cis-retinal ring methyl substituents in visual pigment formation

Artificial visual pigment formation from ring-demethylated retinals was studied in an effort to understand the effect that methyl groups on the chromophore cyclohexenyl ring have on the visual cycle. The stereoselective synthesis of the 11-cis-ring-demethylated analogues involves thallium-accelerated Suzuki cross-coupling reactions and highly stereocontrolled Wittig reactions to form key bonds. Only 11-cis-1,1,5-trisdemethylretinal (2) failed to form an artificial pigment, whilst variable pigment-formation yields were determined for the remaining analogues, increasing with the number (and location) of the chromophore hydrophobic ring methyl groups. Our results with the monodemethylated analogues 11-cis-5-demethylretinal (4) and 11-cis-1-demethylretinal (5) show that the C1-2-CH(3) groups are more important for pigment formation than the C5-CH(3) substituent. This is reflected in the absorption maxima of the artificial pigments, with values closer to that of native rhodopsin for 4. Docking studies based on a rhodopsin crystal structure, however, predict a lower pigment stability for 4 than for 5. Gas-phase DFT (B3LYP/6-31G*) computations of the free-ligand geometries, conformational searches about the C6--C7 bond, and docking studies revealed that, although the conformation of bound 5 is close to that of the native chromophore, the ligand needs to overcome the energy cost of shifting the unbound favored 6-s-trans conformation to the bound 6-s-cis form. In addition, the presence of an extra methyl group at C18 (11-cis-18-methylretinal, 7) is tolerated well and adds further stability to the complex, most probably due to increased hydrophobic interactions.     

Understanding the Molecular Basis of 5-HT4 Receptor Partial Agonists through 3D-QSAR Studies

Alzheimer’s disease (AD) is a neurodegenerative disorder whose prevalence has an incidence in senior citizens. Unfortunately, current pharmacotherapy only offers symptom relief for patients with side effects such as bradycardia, nausea, and vomiting. Therefore, there is a present need to provide other therapeutic alternatives for treatments for these disorders. The 5-HT₄ receptor is an attractive therapeutic target since it has a potential role in central and peripheral nervous system disorders such as AD, irritable bowel syndrome, and gastroparesis. Quantitative structure-activity relationship analysis of a series of 62 active compounds in the 5-HT₄ receptor was carried out in the present work. The structure-activity relationship was estimated using three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques based on these structures’ field molecular (force and Gaussian field). The best force-field QSAR models achieve a value for the coefficient of determination of the training set of R²_training = 0.821, and for the test set R²_test = 0.667, while for Gaussian-field QSAR the training and the test were R²_training = 0.898 and R²_test = 0.695, respectively. The obtained results were validated using a coefficient of correlation of the leave-one-out cross-validation of Q²_LOO = 0.804 and Q²_LOO = 0.886 for force- and Gaussian-field QSAR, respectively. Based on these results, novel 5-HT₄ partial agonists with potential biological activity (pEC₅₀ 8.209–9.417 for force-field QSAR and 9.111–9.856 for Gaussian-field QSAR) were designed. In addition, for the new analogues, their absorption, distribution, metabolism, excretion, and toxicity properties were also analyzed. The results show that these new derivatives also have reasonable pharmacokinetics and drug-like properties. Our findings suggest novel routes for the design and development of new 5-HT₄ partial agonists.     

5-甲酰基-2，4-二甲基-1H-吡咯-3-羧酸的合成与工艺研究

5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸是抗癌药苹果酸舒尼替尼的重要中间体。以乙酰乙酸叔丁酯为起始原料．依次经过Knorr缩合反应、脱羧反应、Vilsmeier反应、水解反应4步反应合成了目标化合物5-甲酰基．2,4-二甲基-1H-吡咯-3-羧酸,总收率55.4%。并对合成工艺进行了优化,适合于工业化生产。     

Studies on amalgam electrodes. The reaction of but-1-yn-3-ol at copper amalgam

The copper amalgam electrode can be used for clean oxidative coupling of but-1-yn-3-ol in good yield. An electrochemically generated intermediate can be further coupled in a solution process by aeration of the electrolyte giving increased yields. Addition of pyridine depresses coulombic yields in the electrochemical system, although it increases the rate of the purely chemical process.     

2,4-二氯苯酚在水中溶解度的测定及关联

在pH值为6.2或9.3条件下,采用综合法测定了2,4-二氯苯酚在水中的固液平衡数据,分别用经验方程、W ilson方程、固液平衡λH方程对实验数据进行了拟合处理。结果说明,在pH值为9.3条件下,2,4-二氯苯酚的水溶解度增大;W ilson方程、λH方程模型均能很好地关联2,4-二氯苯酚的水溶解度数据,pH=9.3时平均相对误差分别为3.00%,1.17%,其中λH方程拟合效果更好。     

Studies on Pollutants. VIII. Trace Analysis of Vanadium with N-p-Methoxyphenyl-2-furohydroxamic Acid

Abstract

A highly sensitive, selective, and rapid method for the spectrophotometric determination of trace amounts of vanadium(V) is described. Vanadium(V) is extracted from 4–8 M hydrochloric acid solutions as its violet complex with N-p-methoxyphenyl-2-furohydroxamic acid (MFHA) in chloroform. The extract shows maximum absorbance at 545 run (E = 7.3 × 10³ L.mole^?1 cm^?1) and obeys Beer's law over the range 0–12 ppm of vanadium; Sandell's sensitivity being 0.007 μg/cm². The method has been applied for the analysis of vanadium in pond water, rock phosphates, and steels.     

3-氯甲基-4-羟基苯乙酮合成工艺研究

利用盐酸作催化剂 ,由对羟基苯乙酮和甲醛经缩合生成 3 氯甲基 4 羟基苯乙酮 ,研究了该中间体合成的配料比、反应温度和反应时间对反应收率的影响。结果表明 :对羟基苯乙酮、甲醛、盐酸配料摩尔比为 1∶2∶5 ,反应温度为 30～ 35℃ ,反应时间为 3 .0h ,反应收率为 80 % ,纯度符合药用标准