在基础化学实验教学过程中如何培养学生“想”的意识——以“经典合成实验”教学为例

本文主要介绍了以经典合成实验"二水二草酸合铜(Ⅱ)酸钾的合成"和"三草酸合铁(Ⅲ)酸钾的合成"为例,与学生一起探讨合成条件对产物的"质"和"量"的影响的过程,并用一张图清晰地展示并引导学生深刻分析了三草酸合铁(Ⅲ)酸钾的合成过程中,学生因缺乏反思、判断的能力而坠入迷途或误入歧途而导致的实验结果不同的原因,以此展现了基础化学实验教学过程中如何培养学生"想"的意识和"批判性"思维。     

5-甲氧基-2-苯基-2, 3-二氢苯并呋喃的制备——介绍一个大学综合化学实验

介绍了一个大学综合化学实验。该实验以对甲氧基苯酚和苯乙烯为原料,六氟异丙醇为溶剂,2,3-二氯-5,6-二氰基-1,4-苯醌为氧化剂,室温合成5-甲氧基-2-苯基-2,3-二氢苯并呋喃,并用IR、1H NMR、13C NMR和HRMS对产物结构进行表征。本实验有益于激发学生的科研兴趣和探索精神,训练学生的综合实验操作技能和分析能力,培养学生的创新思维和科研能力。     

6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯的制备——介绍一个大学药物化学综合实验

介绍了我校制药工程专业和药物制剂专业开展的一个综合药物化学实验,该实验以合成PARP1抑制剂的关键中间体6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯为目标分子,该化合物是作者课题组目前正在研究的PARP1抑制剂的关键中间体,其合成方法是以L-3,4-二甲氧基苯丙氨酸为原料,甲醇为溶剂,二氯亚砜为脱水剂,室温条件下合成L-3,4-二甲氧基苯丙氨酸甲酯,再以多聚甲醛为原料,二氯甲烷为溶剂,三氟乙酸为催化剂,经Pictet-Spengler反应合成6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯,目标化合物的结构使用1H NMR、MS等分析方法进行表征。本实验有益于激发学生独立思考能力和研究意识,训练学生的综合实验操作技能和有机化合物的结构鉴定能力,培养学生掌握药物合成科学研究的基本思路和基本方法。     

托品酮及其衍生物卓柯卡因的合成 ——介绍一个中级有机化学实验

介绍一个面向大学二年级本科生的中级有机化学实验。综合多篇文献选择了一条较为适宜学生实验的连续合成路线：由柠檬酸合成1,3-丙酮二羧酸,经Mannish反应合成托品酮,NaBH。还原得到3-托品醇,最后与苯甲酰氯反应得到卓柯卡因。对实验中的问题进行了讨论。     

肉桂酸的逆合成分析、合成设计及实验制备——一次设计型实验课的探索

以肉桂酸为目标产物,通过逆合成分析、合成设计,采用不同的实验方法合成制备,介绍了水相Heck反应、无溶剂Perkin反应、水相Wittig反应、水相Knoevenagel反应,拓展了学生的合成设计思维。本实验涵盖了目标产物的合成、纯化与表征,让学生认识和完成了一个基本的科研过程,提高了学生的综合能力。     

2,4-二甲基吡咯-3,5-二羧酸二乙酯的合成——推荐一个大学有机化学实验

采用Knorr吡咯合成法，以乙酰乙酸乙酯和亚硝酸钠为原料，在醋酸和锌粉作用下采用“一锅法”得到2,4-二甲基吡咯-3,5-二羧酸二乙酯。本实验涉及到控温、回流、重结晶、熔点测定、红外光谱及核磁共振等实验操作和分析检测方法。该实验原料简单易得、产物收率高，结合波谱解析方法，可以培养和提高学生合成实验的能力，加强学生对杂环合成和波谱解析的理解与分析。     

药学本科实验类型及其教学方法的改革

介绍在药学本科实验类型及其教学方法改革所作的一点探索。在学生实验中以相同的原料、类似的试剂,分别采用传统加热化学合成方法与微波辐射合成方法合成同一药物中间体,引导学生就制备工艺、实验结果的差异进行对比讨论,以提高学生的学习兴趣,保证实验教学质量。     

二次生长法NaA沸石分子筛膜的合成与表征——推荐一个研究型综合实验

介绍一个研究型综合实验——二次生长法NaA沸石分子筛膜的合成与表征。实验预先利用热浸渍法在α-Al_2O_3多孔载体管外表面引入NaA沸石分子筛晶种,再通过二次生长法合成NaA沸石分子筛膜。用扫描电子显微镜和X射线衍射仪表征载体管和NaA沸石分子筛及膜的形貌和结构,并利用渗透蒸发乙醇脱水膜分离装置测试膜的分离性能。通过本实验使学生了解膜分离技术这一科学前沿领域,激发学生对科学研究的兴趣,培养学生的科研探究能力。本实验涵盖合成、表征及性能测试,知识要点多、学科覆盖面广,有利于提升学生的实践操作能力、创新意识和综合运用知识的能力。     

有机化学知识在高分子材料合成创新实验中的运用——分享几个实例

针对目前教学中存在的理论课程之间、实验课程与理论课程之间关联不够紧密等问题,探索了通过"知识关联"将有机化学基本知识运用到高分子材料合成创新实验中的教学思路。以新试剂合成及应用、荧光聚酯合成、聚酰胺合成、聚酯水解等为例,介绍了如何将有机化学新理论、新方法、新试剂应用于本科高分子化学和高分子材料实验教学,以及如何将有机化学的理论知识和实验手段应用于高分子材料合成教学中。实践表明:通过"知识关联",将有机化学基础理论知识和实验技能应用于高分子合成实验中可以提高学生对所学知识的理解和运用能力,增强学生的实验探索兴趣,有效改进了高分子材料合成实验教学的课堂气氛。     

OBE理念下大学生创新实验项目的探究与实践

介绍了OBE教育理念下以“离子型铱配合物的合成及性能研究”作为大学生创新实验训练项目的实施过程。实验内容以2-(4-氟苯基)吡啶、1-(4-氟苯基)异喹啉为主配体,4,4′-二叔丁基-2,2′-联吡啶为中性配体,六氟磷酸根为阴离子合成了2种离子型的铱配合物。2种配合物分别展现出绿光和红光发射,量子效率分别达到85%和73%。整个项目的实施过程以学生为中心,紧密联系科学研究的热点并结合专业理论知识,不仅培养了学生的科研兴趣和创新能力,也锻炼了学生的综合实验能力,取得了较好的学习效果。     

Carbodiimide-mediated preparation of the tricyclic pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine ring system and its application to the synthesis of the potent antitumoral marine alkaloid variolin B and analog

A total synthesis of the marine alkaloid variolin B has been completed in 13 steps in an overall yield of 6.5% from 3-formyl-4-methoxypyridine. Our approach is based on the sequential formation of the 7-azaindole ring, the tricyclic pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine ring system, and finally installation of the 2-aminopyrimidine ring at C5. The required 7-azaindole ring appropriately substituted is formed by a modified indole synthesis involving a nitrene insertion process (two steps). Formation of the annelated pyrimidine ring is achieved by two routes both involving a carbodiimide-mediated cyclization process, which allow incorporation of the amine functionality at C9 of the core tricyclic (six steps). Installation of the northeast 2-aminopyrimidine ring at C5 is performed using the Bredereck protocol (three steps). Ultimate, thermal decarboxylation with concomitant O-methyl deprotection and further N-benzyl deprotection by the action of triflic acid completed the synthesis of the target natural product variolin B.     

A strategy for the synthesis of 2,3-disubstituted indoles starting from N-(o-halophenyl)allenamides

A strategy for the synthesis of 2,3-disubstituted indole derivatives based on an intramolecular carbopalladation-anion capture cascade has been developed, wherein construction of the pyrrole ring and functionalisation of the indole C2 and C3 positions were achieved by extensive use of palladium(0)-catalysed coupling reactions.     

Simple route to 3-(2-indolyl)-1-propanones via a furan recyclization reaction

A simple route to 1-R-3-(2-indolyl)-1-propanones has been elaborated based on recyclization of 2-(2-aminobenzyl)furan derivatives. Being a modification of the Reissert indole synthesis, our approach employs the furan ring as a source of carbonyl function. This approach is general and allows varying of substituents in aromatic ring as well as in 3-position of indole nucleus.     

A novel synthetic route for the total synthesis of (±)-uleine

In this study, a new synthetic route for the total synthesis of (±)-uleine is described. The important step in the synthesis of this alkaloid consists of an intramolecular cyclization of the D ring of the azocino[4,3-b]indole skeleton. Reduction of (N-methyl){3-β-ethyl-4-oxo-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide with borane yielded the corresponding (N-methyl){3-β-ethyl-4-hydroxy-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide, which underwent acid-catalyzed ring closure to produce azocino[4,3-b]indole core. Finally, the synthesis of (±)-uleine was completed through several steps from the azocino[4,3-b]indole core.     

A convergent approach to the mitomycin ring system

[structure: see text]. A novel stereoselective approach to the ring system of the mitomycins is described. The synthesis was based on a convergent strategy involving a stereocontrolled addition of a beta-phenyl silyl enol ether to a pyrroline N-acyliminium ion followed by an intramolecular palladium-catalyzed aryl triflate amination to afford the (9R*,9aR*)-tetrahydropyrrolo[1,2-a]indole ring system.     

Synthesis of indole-5,6- and carbazole-2,3-dicarboxylic acid functional derivatives

Principal synthetic approaches to the synthesis of indole-5,6- and carbazole-2,3-dicarboxylic acid functional derivatives are considered. The first of them consists in the construction of the indole ring from simpler aromatic compounds containing carboxy groups, cyano groups, or an imide fragment with subsequent reductive cyclization of the compounds formed. The second approach is based on the modification of a pyrrole or an indole fragment by the introduction of different functional groups with subsequent intramolecular cyclization to the corresponding heterocycles.     

Furan as a 1,3-diketone equivalent: the second type furan recyclization applied to indole synthesis

A new approach for the synthesis of indole derivatives based on protolytic recyclization of 2-alkyl-5-(2-tosylaminoaryl)-furans is described. The furan ring in this unusual transformation formally serves as a 1,3-diketone equivalent.     

Novel cycloalkene indole carbazole alkaloids via the ring closing metathesis reaction

Methodology for the synthesis of a series of carbocyclic indole carbazole natural product analogs is presented. The chemistry involves construction of the core indole, followed by attachment of double bond tethered side chains of three and four carbon lengths. The bottom carbocyclic ring system is formed through a ring closing metathesis reaction, and allows the installation of four, five, and six member ring sizes.     

Synthesis of aminopyrimidylindoles structurally related to meridianins

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ position.     

Total synthesis of (-)-indolactam V

The total synthesis of protein kinase C activator (-)-indolactam V (IL-V) has been successfully completed with two separate approaches: From known 4-nitrotryptophan derivative 3 in 8 steps (49% overall yield) and from L-glutamic acid in 12 steps (18% overall yield), where 4-nitrotryptophanol derivative 4 served as a key intermediate. Derivatives 3 and 4, both incorporating indole 4-substitution and the C-9 stereocenter in IL-V, were synthesized via the Pd-catalyzed indole synthesis from 3-nitro-2-iodoaniline 5 with aldehydes 6 and 7, respectively. Aldehyde 7 was, meanwhile, synthesized from l-glutamic acid in 5 steps (68% yield). Lactamization of the 9-membered ring was achieved using HATU in THF in good yield.