毛细管胶束电动色谱在扁桃酸合成中的应用

扁桃酸是药物中间体,可以苯甲醛为原料在相转移催化剂作用下合成制得.为了选择最佳合成条件,提高扁桃酸的转化率,需要对合成过程中各组分的含量进行快速测定,及时指导最优合成条件的选择.产品扁桃酸中可能含有未反应的苯甲醛和副产品苯甲酸、苯甲醇等杂质.以往采用非水溶剂酸碱滴定分析法测定产品中扁桃酸的含量,但当产品中有苯甲酸等酸性物质存在时,会使测定结果偏高.由于待测样品中组分扁桃酸、苯甲酸酸性使沸点较高,     

有机化学反应中海水替代淡水试验的初步探讨

分别使用淡水和海水进行了乙酰苯胺和扁桃酸的制备、康尼查罗反应和霍夫曼重排等5个反应研究。结果表明,某些反应可以直接用海水替代淡水进行,如邻氨基苯甲酸的制备,产率为77.2%,与应用淡水的文献值接近;某些反应可由海水经简单处理后替代淡水进行,如苯甲醛的康尼查罗反应,产率为52.2%,与应用淡水的文献值接近;而2-氯-3-氨基-4-甲基吡啶的制备实验,产率为98.1%,优于应用淡水的文献值;而乙酰苯胺和扁桃酸的制备使用海水或经简单处理后的海水的实验结果均不理想。     

Preparation of chitosan‐based molecularly imprinted material for enantioseparation of racemic mandelic acid in aqueous medium by solid phase extraction

An S‐mandelic acid imprinted chitosan resin was synthesized by cross‐linking chitosan with glutaraldehyde in 2% acetic acid solution. S‐Mandelic acid imprinted chitosan resin was used to enantioselectively separate racemic mandelic acid in aqueous medium. When keeping the pH of sample solution (100 mM Tris‐H₃PO₄) at 3.5 and adsorption time at 40 min, the enantiomer excess of mandelic acid in supernatant was 78.8%. The adsorption capacities of S‐mandelic acid imprinted chitosan resin for S‐ and R‐mandelic acid were determined to be 29.5 and 2.03 mg/g, respectively. While the adsorption capacities of non‐imprinted cross‐linked chitosan for S‐ and R‐mandelic acid were 2.10 and 2.08 mg/g, respectively. The result suggests that the imprinted caves in S‐mandelic acid imprinted chitosan resin are highly matched with S‐mandelic acid molecule in space structure and spatial arrangement of action sites. Interestingly, the enantiomer excess value of mandelic acid in supernatant after adsorption of racemic mandelic acid by R‐mandelic acid imprinted cross‐linked chitosan was 25.4%. The higher enantiomer excess value by S‐mandelic acid imprinted chitosan resin suggests that the chiral carbons in chitosan and the imprinted caves in S‐mandelic acid imprinted chitosan resin combine to play roles for the enantioselectivity of S‐mandelic acid imprinted chitosan resin toward S‐mandelic acid. Furthermore, the excellent enantioselectivity of S‐mandelic acid imprinted chitosan resin toward S‐mandelic acid demonstrates that using chiral chitosan as functional monomer to prepare molecularly imprinted polymers has great potential in enantioseparation of chiral pharmaceuticals.     

D/L扁桃酸的合成研究

对D／L扁桃酸的合成工艺进行了优化,尤其在溶剂的选择与回收,二氯化物的制备以及产品的纯化与提取等方面作了有效的改进,收率与纯度有很大改善,分别达到80％和99．4％。     

Fe2(SO4)3·xH2O CATALYTIC ESTERIFICATION OF MANDELIC ACID WITH ALCOHOLS

Mandelates have played an important role in organic synthesis and are used in artificial flavorings and perfumes. Mandelates may be prepared as follows:1). Direct esterification of mandelic acid with alcohols in the presence of sulfuric acid^1,2 or 2,2-dimethoxypropane and sulfuric acid;³ 2). Treatment mandelic acid and iodide in the presence of sodium hydrogen carbonate;⁴ 3). Treatment mandelic acid and alcohols with thionyl chloride.⁵ But these methods have some advantages and are not universally applicable. For example, the direct esterification catalyzed by sulfuric acid is not suitable for acid sensitive compounds and has the disadvantages of the corrosivity of strong acid and usually accompanying side reactions such as carbonization,oxidation, etherification, etc. We now reported the catalytic esterification of mandelic acid with a serious of alcohols using Fe₂(SO₄)₃·xH₂O as a new convenient catalyst.     

Nucleophilic benzoylation using a mandelic acid dioxolanone as a synthetic equivalent of the benzoyl carbanion. Oxidative decarboxylation of alpha-hydroxyacids

The synthesis of alkyl aryl ketones using a mandelic acid dioxolanone as a synthetic equivalent (Umpolung) of the benzoyl carbanion is reported. The methodology involves alkylation of the mandelic acid dioxolanone, hydrolysis of the dioxolanone moiety in the alkylated products and oxidative decarboxylation of the resulting alpha-hydroxyacids. The last step is carried out in a catalytic aerobic way using a Co (III) complex in the presence of pivalaldehyde under very mild conditions.     

Silica sulfuric acid as a highly efficient catalyst for the synthesis of diarylacetic acids

An efficient heterogeneous method for the synthesis of diarylacetic acids was developed utilizing silica sulfuric acid as a catalyst. The reaction is highly efficient with a small amount of catalyst for the combination of a variety of electron-neutral to electron-rich arenes with glyoxylic acid. The reaction can also be utilized to synthesize unsymmetric derivatives from activated mandelic acids in good to excellent yields.     

Synthesis of deoxy sugar esters: a chemoenzymatic stereoselective approach affording deoxy sugar derivatives also in the form of aldehyde

A chemoenzymatic synthesis of deoxy sugar esters is described. The synthesis is based on the O-alkylation of carboxylic acid with 2-bromo-5-acetoxypentanal. The method allows treatment of hydroxy carboxylic acids without protection of alcoholic hydroxyl groups. Several stereoisomeric deoxy sugar esters were resolved (up to ee or de > 98%) using a lipase-catalyzed acetylation of hemiacetals that in certain cases afforded deoxy sugar derivatives in the form of aldehydes. The stereochemistry of the reactions was determined by the NMR spectra of mandelic acid derivatives.     

AN EFFICIENT AND CONVENIENT PROCEDURE FOR PREPARATION OF MANDELATES CATALYSED BY TiO2/SO2− 4 SOLID SUPERACID

An easy and efficient synthesis of mandelates in excellent yields from mandelic acid with alcohols catalysed by TiO₂/SO^2? ₄ solid superacid.     

Iodide-catalyzed reductions: development of a synthesis of phenylacetic acids

A new convenient and scalable synthesis of phenylacetic acids has been developed via the iodide catalyzed reduction of mandelic acids. The procedure relies on in situ generation of hydroiodic acid from catalytic sodium iodide, employing phosphorus acid as the stoichiometric reductant.     

Fluorescent sensors for the enantioselective recognition of mandelic acid: signal amplification by dendritic branching

Novel chiral bisbinaphthyl compounds have been synthesized for the enantioselective fluorescent recognition of mandelic acid. By introducing dendritic branches to the chiral receptor unit, the fluorescence signals of the receptors are significantly amplified because of the light-harvesting effect of the dendritic structure. This has greatly increased the sensitivity of the sensors in the fluorescent recognition. Study of the three generation sensors demonstrates that the generation zero sensor is the best choice for the recognition of mandelic acid because of its greatly increased fluorescence signal over the core and its high enantioselectivity. This sensor is potentially useful for the high throughput screening of chiral catalysts for the asymmetric synthesis of alpha-hydroxycarboxylic acids.     

Chiralpak AD-H和Chiralcel OJ-H手性固定相拆分扁桃酸系列化合物

对比了商品化的淀粉型手性固定相Chiralcel OJ-H和纤维素型手性固定相Chiralpak AD-H柱在正相条件下对扁桃酸系列8个化合物的拆分,结果表明Chiralcel OJ-H柱对扁桃酸系列化合物具有更强的手性识别能力,8个外消旋扁桃酸化合物在36 min内都得到了基线分离。研究发现,扁桃酸苯环上的取代基对其拆分的难易程度影响很大,其电子诱导效应影响扁桃酸类化合物在固定相上的保留时间,其空间位阻效应是扁桃酸在固定相上被拆分成败的决定因素。通过对比分析扁桃酸和手性柱的结构,探讨了可能的手性拆分机理是基于Chiralpak AD-H(Chiralcel OJ-H)手性固定相和扁桃酸系列化合物之间的氢键-氢键、偶极-偶极、π-π电子相互作用以及空间适应性等诸多因素的综合影响,其中空间适应性起到至关重要的作用。本研究可为一些实际光学活性扁桃酸及其类似物的对映体纯度测定与拆分研究提供参考。     

Convenient synthesis of O-functionalized mandelic acids via Lewis acid mediated transformation of 1,3-dioxolan-4-ones

An efficient method for the synthesis of O-substituted mandelic acids containing alkenyl, alkynyl, methoxycarbonyl, or phenacyl fragments via the Lewis acid-catalyzed reaction of 1,3-dioxolan-4-ones with different C-nucleophiles is proposed.     

A remarkable iodine-catalyzed protection of carbonyl compounds

We report here a remarkably simple molecular iodine-catalyzed protection method for various carbonyl compounds as ketals in a general reaction. The iodine-catalyzed reaction of mandelic acid and lactic acid with several aldehydes has furnished a highly diastereoselective synthesis of cis and trans dioxolanones.     

Asymmetric addition of arylboronic acids to glyoxylate catalyzed by a ruthenium/Me-BIPAM complex

The enantioselective synthesis of α-hydroxy esters by ruthenium-catalyzed 1,2-addition of arylboronic acids to tert-butyl glyoxylate is described. The use of RuCl(2)(PPh(3))(3) with (R,R)-Me-BIPAM gave optically active mandelic acids of up to 99% ee. Addition of a fluoride salt such as potassium fluoride (KF) or caesium fluoride (CsF) was effective for achieving high enantioselectivities.     

温度诱导双水相体系中扁桃酸的手性识别研究

以双水相体系为手性识别体系, 研究了异丙醇/盐和TritonX-114温度双水相体系中扁桃酸的分配行为. 对于醇/盐体系, 扁桃酸均倾向于分配在醇相中, 不适合作为手性识别系统; 而对于TritonX-114温度双水相体系, 扁桃酸富集于水相, 适合作为手性识别系统. 以L-酒石酸正戊酯和β-环糊精作为手性识别剂, 对TritonX-114/L-酒石酸正戊酯、TritonX-114/L-酒石酸正戊酯/茶皂素和TritonX-114/β-环糊精3个识别体系的研究发现, TritonX-114/L-酒石酸正戊酯/茶皂素和TritonX-114/β-环糊精体系中, 手性识别效果明显, 最佳分离体系为: 茶皂素含量0.51 mmol, L-酒石酸正戊酯含量1.4 mmol, 温度55 ℃, 最大分离因子1.29.     

Concise Stereoselective Total Synthesis of Leiocarpin C

A simple and highly concise strategy has been developed for the stereoselective total synthesis of leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO₄‐catalyzed cis‐hydroxylation and selective reduction with K‐Selectride as key steps.     

The dimethyldioxirane-mediated oxidation of phenylethyne

The product pattern found for the dimethyldioxirane-mediated oxidation of phenylethyne strongly depends on the reaction conditions. Dimethyldioxirane generated in situ from caroate (HSO(5)(-)) and acetone in acetonitrile-water furnishes phenylacetic acid as the main product. With solutions of dimethyldioxirane in acetone, mandelic acid and phenylacetic acid are mainly formed. The relative abundances of the two acids depend on the residual water present in the dimethyldioxirane-acetone solution. Application of thoroughly dried solutions of the reagent effects increased formation of mandelic acid. When phenylethyne is oxidized by dimethyldioxirane transferred into tetrachloromethane, to minimize traces of water even further, oligomeric mandelic acid is obtained. The results are rationalized by the initial formation of phenyloxirene, which is known to equilibrate with phenylformylcarbene and benzoylcarbene. Subsequent Wolff rearrangement produces intermediate phenylketene, which can be trapped by water as phenylacetic acid or suffer from further oxidation to the alpha-lactone of mandelic acid. The alpha-lactone can either react with water to yield mandelic acid or, under anhydrous conditions, to yield oligomeric mandelic acid. In addition to mandelic acid and phenylacetic acid phenylglyoxylic acid, benzoic acid and benzaldehyde are observed as reaction products. The formation of phenylglyoxylic acid by transfer of two oxygen atoms to the unrearranged carbon skeleton of phenylethyne followed by oxygen insertion into the aldehydic C-H bond of the intermediately formed phenylglyoxal is discussed. In a second pathway this acid is formed by partial oxidation of mandelic acid. Benzaldehyde and benzoic acid are explained as products of the oxidative degradation of the alpha-lactone by dimethyldioxirane. Under in situ conditions benzoic acid is also formed by caroate initiated oxidative decarboxylation of phenylglyoxylic acid and/or intermediate phenylglyoxal.     

The oxidation of organic substances by compounds of tervalent manganese-I Oxidation of mandelic acid, ethylene glycol, glycerol and d-mannitol by the pyrophosphate complex of manganese(III) and by manganese(III) sulphate

The oxidation of mandelic acid, ethylene glycol, glycerol and d-mannitol by the pyrophosphate complex of manganese(III) and with manganese(III) sulphate was studied. It was shown that benzaldehyde is formed by oxidation of mandelic acid, which undergoes no further oxidation. In the case of ethylene glycol, glycerol and d-mannitol the reactions do not follow a simple course and therefore are not of analytical utility. The effect of acidity and time on the course of the reactions was found and a procedure for the indirect titrimetric determination of mandelic acid with both reagents proposed.     

Enantioselective α-alkylation of piperidine via chiral perhydropyrido [2,1-b] [1,3,4]-oxadiazinone: An easy route for the synthesis of both enantiomers of coniine

Enantioselective direct alkylation of piperidine involving chiral perhydropyrido [2,1-b] [1,3,4]-oxadiazinone using either form of mandelic acid as chiral auxiliary is reported. The application of the strategy is demonstrated by the synthesis of (R)- as well as (S)- coniine.