使用 N,N-二异丙基乙胺碱合成 N,N,N-三甲基壳聚糖的实验设计优化。

IF 2.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Carbohydrate Research Pub Date : 2024-10-16 DOI:10.1016/j.carres.2024.109289
Vivien Nagy , Bergthóra S. Snorradóttir , Héléne Liette Lauzon , Már Másson
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引用次数: 0

摘要

本研究介绍了一种新型的 N,N,N-三甲基壳聚糖(TMC)合成方法,该方法通过使用非亲核碱和优化溶剂系统来提高可扩展性,同时解决了粘度管理和搅拌效率等关键因素。研究目标还包括在尽量减少试剂用量的同时,实现高度的 N,N,N-三甲基化,而不发生 O-甲基化。研究人员探索了八种碱、三种溶剂系统和不同程度的稀释,以减轻粘度挑战和气体演化。使用 1H NMR 光谱分析了 TMC 产物的特征。3.3、3.0 和 2.8 ppm 处峰值的积分值(对应于三甲基、二甲基和单甲基)用于量化甲基化程度。以 N,N-二异丙基乙胺(DIPEA)为碱,DMF 为溶剂得到了最有希望的初步结果。使用相对于壳聚糖的 6 等量碘甲烷(MeI)和 DIPEA 作为碱,实现了高达 68% 的 DTM。应用实验设计(DoE),在稀释条件下对该方法进行了进一步优化,这对工业规模化和粘度控制至关重要。全因子设计(32)的结果表明,稀释介质可有效防止粘度问题,使反应混合物的粘度明显降低到 5.9 cP,与最初的实验相比,粘度降低了 16 倍。实验还确定,MeI 试剂和碱添加量都是影响 DTM 反应的重要因素,这两个因素都呈现二次方效应。DoE 模型显示出较高的显著性(R = 0.97)、较高的未来预测精度(Q2 = 0.87)、良好的模型有效性(0.84)和出色的重现性(0.96)。这些结果标志着 TMC 合成技术的显著进步,提供了一种高效实用的方法,对工业应用具有重要意义。
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Design of experiments optimization of N,N,N-trimethyl chitosan synthesis using N,N-diisopropylethylamine base
This study presents a novel synthesis method of N,N,N-trimethyl chitosan (TMC) by using a non-nucleophilic base and optimizing the solvent system for enhanced scalability, while addressing critical factors such as viscosity management and stirring efficiency. The study objectives also included achieving high N,N,N-trimethylation without O-methylation while minimizing reagent use. Eight bases, three solvent systems, and varying levels of dilution were explored to mitigate viscosity challenges and gas evolution. 1H NMR spectroscopy was used to characterize the TMC products. The integral values of the peaks at 3.3, 3.0, and 2.8 ppm, corresponding to trimethyl, dimethyl, and monomethyl groups, were used to quantify the methylation degrees. The most promising initial results were obtained with N,N-diisopropylethylamine (DIPEA) base, and DMF as solvent. Using 6 eq methyl iodide (MeI) relative to chitosan and DIPEA as base, up to 68 % DTM was achieved. Applying Design of Experiments (DoE), the method was further optimized under diluted conditions, crucial for industrial scalability and viscosity control. Results from a full factorial design (32) revealed that diluted medium effectively prevented viscosity concerns, achieving a notably low viscosity of 5.9 cP in the reaction mixture, a 16-fold decrease in viscosity, compared to initial experiments. It was also established that both the MeI reagent and the base addition are significant factors for the DTM response, with both factors showing quadratic effects. The DoE model demonstrated high significance (R = 0.97), high precision for future prediction (Q2 = 0.87), good model validity (0.84) and excellent reproducibility (0.96). The results mark a notable advancement in TMC synthesis, offering an efficient and practical method with significant implications for industrial applications.
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来源期刊
Carbohydrate Research
Carbohydrate Research 化学-生化与分子生物学
CiteScore
5.00
自引率
3.20%
发文量
183
审稿时长
3.6 weeks
期刊介绍: Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".
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