Biomass Group, Nanjing Agricultural University, PO Box 68, 40 Dianjiangtai Road, Nanjing 210031

Cycloamination strategies for renewable N-heterocycles

Recently, Dr. H Li and Prof. Zhen Fang, collaborated with Prof. RL Smith Jr. (Tohoku University, Japan), published a review (Spotlight) paper in Green Chemistry about the production of renewable N-heterocycles.

Biomass resources have infinite possibilities for introducing nitrogen, sulfur, or phosphorus heteroatoms into their structures by virtue of controllable carbon-heteroatom bond formation. In this review, cycloamination approaches for thermal (catalyst-free) and catalytic transformation of biomass feedstocks into N-heterocyclic molecules including mechanistic pathways are analyzed. Bottom-up (small molecule substrates) and top-down (large molecule substrates) are considered. Sustainable routes for synthesis of five-membered (pyrroles, pyrrolidones, pyrazoles, imidazoles), six-membered (pyridines, pyrazines), fused (indoles, benzimidazoles), and other relevant azaheterocycles are critically assessed. Production of biomass-derived six-, seven-, and eight-membered as well as fused N-heterocyclic compounds with present approaches have relatively low selectivities. Attention to methods for forming analogous sulfur or phosphorus heteroatom compounds from biomass resources using either bottom-up or top-down strategies appear to have been greatly overlooked. Synthetic auxiliaries (heating modes, nitrogen sources) that enhance reaction efficiency and tunability of N-heterocyclic ring size/type are considered and plausible reaction mechanisms for pivotal pathways are developed.

Efficient amination strategies for synthesis of N-heterocycles from functional molecules (bottom-up) or from biomass (top-down) via sustainable C-N/C-X bond chemistry （从功能分子(自下而上)或从生物质(自上而下)通过可持续碳- n /C-X键化学合成n杂环的高效胺化策略）

Related results were accepted in Green Chemistry:

H Li*, HX Guo, Zhen Fang*, TM Aida, RL Smith Jr*, Cycloamination Strategies for Renewable N-heterocycles, Green Chemistry, https://doi.org/10.1039/C9GC03655E , 22, 582-611, 2020 (Spotlight Paper, Review).

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李虎博士在国际学术期刊Green Chemistry发表学术论文

可再生氮杂环的环胺化策略

最近，国际学术期刊Green Chemistry（影响因子9.4, Q1，第一署名单位为南京农业大学，第一作者为李虎博士，通讯作者为李虎博士,方真教授和日本东北大学RL Smith Jr教授）以Spotlight paper形式，发表了生物质生产可再生氮杂环化合物的综述。

生物质资源通过可控的碳-杂原子成键将氮、硫、磷等杂原子引入其结构中具有无限的可能性。本文综述了近年来生物质原料热(无催化)和催化转化为n -杂环分子的环胺化方法及其机理。考虑自底向上(小分子底物)和自顶向下(大分子底物)。五元(吡咯、吡咯烷酮、吡唑、咪唑)、六元(吡啶)的合成路线。用现有方法生产生物衍生的六元、七元、八元以及融合的n杂环化合物的选择性较低。利用自底向上或自顶向下的战略从生物量资源中形成类似硫或磷杂原子化合物的方法似乎受到了极大的忽视。考虑了提高反应效率和n杂环尺寸/类型可调性的合成助剂(加热方式、氮源)，并建立了关键途径的合理反应机制。

详情可见：

H Li*, HX Guo, Zhen Fang*, TM Aida, RL Smith Jr*, Cycloamination Strategies for Renewable N-heterocycles, Green Chemistry (IF 9.4), https://doi.org/10.1039/C9GC03655E 22, 582-611, 2020 (Spotlight Paper, Review).

Prof. Charles Xu from University of Western Ontario visited our Lab

On November 14, 2019, as invited by Prof. Zhen Fang, Prof. Charles Chunbao Xu from University of Western Ontario (UWO) in Canada and Dr. Yongsheng Zhang from Zhengzhou University visited our College of Engineering for the academic exchanges and research collaborations. Prof. Xu has a close collaboration with Prof. Fang for a long history in research and student exchanges.

In the afternoon, Prof. Xu gave a lecture to teachers and students on “Conversion of agricultural biomass into bio-based chemicals and materials”. He briefly introduced about UWO and its main research directions, including the works on biomass resources, sludge into bioenergy, biofuels and bio-based chemicals, and presented his Lab’s main research topics and results in detail, particularly showed us how to produce economic viable materials and chemicals besides biofuels from biomass wastes. The academic lecture brings inspiration to the future development and directions of renewable energy and biomass resources utilizations.

After the presentation, Prof. Xu and Dr. Zhang visited our laboratory guided by Prof. Fang. Prof. Fang gave a detailed introduction about the main research directions, research progress and various instruments of the laboratory.

Professor Chunbao Xu, fellow of the Canadian Academy of Engineering and a tenured professor of the Department of Chemical Engineering at UWO in Canada, is a world-renown expert in the field of biomass refining. He is the Co-editor-in-chief of the International Journal of Chemical Reaction Engineering (IJCRE, an SCI Journal). In recent years, he has published nearly 200 papers in International academic journals with 7,700 cites and H index of 47.

加拿大工程院院士徐春保教授一行来访我院

2019年11月14日，应方真教授邀请，加拿大西安大略大学徐春宝教授和郑州大学张永生博士一行来访我院，进行学术交流与科研合作。徐教授与方教授在科研和学生交流方面有着长期的密切合作。

下午，徐春保教授为我院师生作了“Conversion of agricultural biomass into bio-based chemicals and materials”的专题报告，详细介绍了加拿大西安大略大学历史和主要研究方向，包括生物质、有机固废和污泥转化为生物能源、生物燃料和生物基化学品等方面的研究。特别向我们展示了如何利用农业生物质废弃物生产生物燃料以外的经济可行的材料和化学制品。本次学术讲座对可再生能源和生物质资源利用的未来发展和方向具有启发意义。

报告结束后，徐春保教授一行在方真教授的带领下参观了我们实验室，方老师为其详细介绍了目前实验室的主要研究方向、研究进展及实验室的各种仪器设备。

徐春保教授，现为加拿大工程院院士、加拿大西安大略大学化工系终身教授，生物质精炼领域的世界著名专家。担任SCI期刊化学反应工程国际期刊（IJCRE）的共同总编辑。近年来在学术期刊上发表论文近200篇，被引用7700余次，H因子47。

Prof. Sarani Zakaria from UKM (Malaysia) visited our Lab

As invited by Prof. Zhen Fang, in the morning of October 5^th, 2019, Prof Sarani Zakaria from Universiti Kebangsaan Malaysia (UKM; Bangi, Malaysia), visited our Lab. Prof. Fang gave a detailed introduction of the current research areas, research progress, and how to use the related instruments and equipment in our lab.

Prof. Z Fang has a long-term cooperative relationship with Prof. Zakaria’s group at UKM and co-supervised 4 PhD students (Drs. Fei Ling Pua, Siew Xian Chin, Suet Pin Fan, Umar Adli Bin Amran) and co-authored some research articles since 2011. He hopes that this visit will further enhance friendship and deepen cooperation in research, promote the development of international student exchanges and other activities, particularly jointly apply for research grants from different sources such as “One Belt and One Road”.

国立马来西亚大学Zakaria教授访问生物能源组

2019年10月05日上午，国立马来西亚大学Sarani Zakaria教授应方老师邀请来南京农业大学生物能源组访问和交流。Sarani Zakaria教授一行在方真教授带领下参观了生物能源实验室，方老师为其详细地介绍了目前实验室相关研究方向、研究进展以及相关仪器和设备的使用方法和功能。

方教授与Zakaria教授在马来西亚国立大学的团队有着长期的合作关系，自2011年以来，两人共同培养了4名马来西亚博士生(Fei Ling Pua潘慧琳小姐, Siew Xian Chin陈秀娴小姐, Suet Pin Fan范雪彬小姐, Umar Adli Bin Amran先生)，同时也合作撰写了一些研究论文。方老师和Zakaria教授希望通过此次访问，能够进一步增进两团队的友谊，促进国际学生交流等活动的发展；深化科研合作，特别是联合申请不同渠道的科研资助，例如国家积极响应的“一带一路”建设工程项目。

Prof. RL Smith Jr. and Dr. HX Guo from Tohoku University (Japan) gave lectures

As invited by Prof. Zhen Fang, from September 24^th to 26^th, 2019, Prof. Richard Lee Smith, Jr. and Assistant Prof. Haixin Guo from the School of Environmental Sciences, Supercritical Fluids Center, Tohoku University (Japan), visited our College of Engineering.

In the morning of September 25^th, the chair of Agricultural Mechanization Department & Traffic and Vehicle Engineering Department, Prof. Ruiyin He; Professor Zhen Fang; the deputy director of the International Office of College, Mr. Biao Guo; and Dr. LJ Xu, met with Prof. Smith and Dr. HX Guo in Room C302, Yuxian Building. Mr. B Guo welcomed the arrival of Prof. Smith and Dr. HX Guo. He briefly introduced the current situation and history of the college from the aspects of college scale, subject setting, scientific research, international exchange and cooperation. Prof. RY He said that Prof. Z Fang has a long-term cooperative relationship with Supercritical Fluid Center at Tohoku University. He hopes that this visit will further enhance friendship and deepen cooperation in research, promote the development of international student exchanges and other activities, particularly to jointly host the 2020 “6^th International Symposium & Exhibition on Aqua Science and Water Resources” (ISASWR-2020) holding in our college (Nanjing, Pukou).

Prof. Smith thanked the College for the hospitality. He gave a detailed introduction about Supercritical Fluid Center, Tohoku University, and its research fields, including supercritical fluid technology, green chemical processes, and also showed the research results in the field of green chemical processes for energy, food, chemicals and materials. He said that he hopes to deepen the inter-school cooperation relationship with our college in research and promote the exchange of teachers and students. Finally, he presented the key topics for the upcoming “ISASWR-2020” and both sides had a brief discussion.

In the afternoon of September 25^th, Prof. Smith and Dr. HX Guo gave two invited lectures to teachers and students on “Green Chemical Processes for Energy, Food, Chemicals and Materials” and “Catalytic Systems with Ionic Liquid Additives for the Production of Platform Chemicals and Biofuels”, respectively. The academic lectures bring new enlightenment to the audiences on the directions of renewable energy and resources research and development.

Professor Richard Lee. Smith, Jr, obtained his Bachelor, Master and Ph.D. degrees in Chemical Engineering from Georgia Institute of Technology, USA. He is Professor of Supercritical Fluid Center, School of Environmental Sciences at Tohoku University (Sendai, Japan), specializing in thermodynamics, physical properties, supercritical fluids, and green processes. He is also the Region Editor (Asia) of the Journal of Supercritical Fluids and the editorial board member of Springer Book Series – Biofuels and Biorefineries. He has published more than 260 papers, patents and book chapters with H index of 48.

Dr. Haixin Guo, Female, Assistant Professor of Supercritical Fluid Center, School of Environmental Sciences, Tohoku University, Japan. She is committed to work in green chemistry, biomass resources that are transformed into high value-added chemicals with supercritical fluid-ionic liquid technology, separation engineering and other green chemical processes. In 2012 she obtained master degree in environmental engineering from Nankai University and in 2018 received doctorate in environmental science from Tohoku University. In April 2018, she worked at the Supercritical Fluid Center of Tohoku University and in May was quickly promoted to Assistant Professor of Environmental Science at Tohoku University.

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日本东北大学环境科学学院Smith教授一行来访我院

2019年9月24日-26日应方真教授邀请，日本东北大学环境科学学院Richard Lee. Smith, Jr教授和郭海心助理教授应邀来访我院。9月25日上午，农业机械化系/交通与车辆工程系主任何瑞银教授、方真教授、工学院办公室副主任郭彪等在育贤楼C302会见了Smith教授一行。

郭彪副主任对Smith教授和郭海心助理教授的到来表示欢迎。他从办学规模、学科设置、科学研究、国际交流与合作等方面简要介绍了学院基本情况。何瑞银表示，方真教授与日本东北大学环境科学学院有着长期合作关系，希望借此来访能够进一步增进友谊、深化合作，共同推进2020“第六届水科学与水资源国际研讨暨展览会”(ISASWR-2020) 在我院的举办，并推动国际学生交换等项目的开展。

Smith教授感谢学院的热情接待，详细介绍了日本东北大学超临界流体中心，及其实验室涉及的研究领域，包括超临界流体技术、绿色化学过程等，同时也展示了实验室在能源、食品、化工和材料的绿色化工过程领域的研究成果。他表示，希望与我院深化校际合作关系，增进师生交流。

9月25日下午，Smith教授和郭海心助理教授分别为我院师生作“Green Chemical Processes for Energy, Food, Chemicals and Materials”“离子液体催化生物质转化的机理研究”的专题报告。学术报告为学院师生带来许多关于新能源研究和发展方向的新启示。

Richard Lee. Smith, Jr教授，美国佐治亚理工学院化学工程学士、硕士和博士。日本东北大学环境科学学院超临界流体中心教授，致力于热力学、物理特性、超临界流体和绿色过程等方面研究。兼任Journal of Supercritical Fluids杂志亚洲地区主编以及Springer Nature，Biofuels and Biorefineries系列丛书编委。他发表了260余篇论文、专利和书章节等，H指数为48。

郭海心博士（女），日本东北大学环境科学学院超临界流体中心助理教授。致力于绿色化学，生物质资源转化为高附加值的化学品、超临界流体-离子液体技术、分离工学等方面研究。分别于2012年和2018年获得南开大学环境工程硕士学位和日本东北大学先端环境创成学专业博士学位。2018年4月于日本东北大学超临界流体中心任职，5月升任为日本东北大学环境科学学院助理教授。

High-Concentrated Substrate Enzymatic Hydrolysis of Pretreated Rice Straw with Glycerol and Aluminum Chloride at Low Cellulase Loadings

Based on a central composite design, glycerol and AlCl₃ pretreated rice straw with 0.08 mol/L AlCl₃ at 146.8 °C for 20 min, resulting in 83% delignification, 94% hemicellulose removal, and 92% cellulose recovery for a remarkable glucose yield of 65.7% at high solid loads (15%) and low cellulase loading (3.3 FPU/g dry substrate) with adding Tween 80 (40 mg/g substrate). (通过响应面优化，在146.8 °C和0.08 mol/L AlCl₃条件下，水稻秸秆经甘油-氯化铝预处理20 min后，保留92%的纤维素，同时去除83%的木质素和94%的半纤维素；3 FPU/g干基质和15%基质浓度条件下，添加40 mg/g 干基 Tween 80，酶水解48 h，预处理后水稻秸秆的酶解率可达到65.7%。)

Recently, PhD student Mr. Song Tang supervised by Prof. Zhen FANG developed a glycerol and aluminum chloride pretreatment for lignocellulosic biomass. Rice straw was pretreated with glycerol and AlCl₃ for enzymatic hydrolysis at low cellulase loadings. Based on a central composite design, 83% delignification, 94% hemicellulose removal, and 92% cellulose recovery (or 76% cellulose in solid residue) were achieved under the optimized pretreatment conditions (0.08 mol/L AlCl₃ as catalyst at 146.8 °C for 20 min with 90% glycerol). During glycerol-AlCl₃ pretreatment, the lignin-carbohydrate complex was depolymerized, resulting in the complex and recalcitrant construction of straw effectively being destroyed. The enzyme adsorption ability of pretreated straw was 16.5 times that for the original sample. After pretreatment, glucose yield was increased by 2.4 times to 74% for 48 h. Moreover, concentrated solid (15%) with low cellulase loading (3.3 FPU/g dry substrate) achieved 58.6% glucose yield, and further increased by 12% to 65.7% by adding Tween 80.

The results were published:

S Tang, Q Dong, Zhen Fang*, WJ Cong, ZD Miao, High-Concentrated Substrate Enzymatic Hydrolysis of Pretreated Rice Straw with Glycerol and Aluminum Chloride at Low Cellulase Loadings, Bioresource Technology, 294, 122164 (2019).

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甘油和氯化铝预处理水稻秸秆用于低纤维素酶载量条件下高基质浓度酶水解

最近，博士生唐松（男）同学在方老师的指导下，开发出一种应用于木质纤维素生物质的甘油-氯化铝预处理技术，其对木质纤维素组分分离具有极好的选择性。通过响应面优化，水稻秸秆在146.8 °C和0.08 mol/L AlCl₃条件下，处理20 min后，92%的纤维素被保留，83%的木质素和94%的半纤维素被去除。同时，固体残渣中纤维素含量达到76%。在甘油-AlCl₃预处理过程中，木质素-碳水化合物形成的复合物被解聚，导致秸秆复杂和顽固的结构被有效地破坏。水稻秸秆经预处理后，对纤维素酶的吸附能力提高了16.5倍，酶解率较原始水稻秸秆提高2.4倍，达到了74%。此外，在3 FPU/g和15%基质浓度条件下，酶水解48 h，预处理后水稻秸秆的酶解率达到58.6%，且添加40 mg/g 干基 Tween 80后，提高了12%，达到65.7%。

结果发表在Bioresource Technology:

S Tang, Q Dong, Zhen Fang*, WJ Cong, ZD Miao, High-Concentrated Substrate Enzymatic Hydrolysis of Pretreated Rice Straw with Glycerol and Aluminum Chloride at Low Cellulase Loadings, Bioresource Technology, 294, 122164 (2019).