CN116444418A - 一种仿酶催化氧化断裂叔胺c-n键的方法 - Google Patents
一种仿酶催化氧化断裂叔胺c-n键的方法 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
- B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
- B01J2531/025—Ligands with a porphyrin ring system or analogues thereof, e.g. phthalocyanines, corroles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/70—Complexes comprising metals of Group VII (VIIB) as the central metal
- B01J2531/72—Manganese
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
Abstract
本发明公开了一种仿酶催化氧化断裂叔胺C‑N键的方法，属于化学与工程技术领域。本发明以芳基叔胺类化合物为原料，利用廉价金属Fe、Mn为卟啉活性中心，转化氧气为过氧结构与四价Fe、Mn的络合物；利用NHPI等助催化剂活化底物N‑亚甲基为自由基；二者协同作用下生成苯甲醛等苄基氧化产物，实现C‑N键的选择性断裂，生成咔唑等仲胺产物。本发明解决了现有断裂叔胺C‑N键困难，反应条件苛刻的问题，有效提高C‑N键断裂产物咔唑的产率，同时采用绿色的氧气、过氧化氢等氧化剂即可实现C‑N键断裂，具有绿色温和的特点。
Description
技术领域
本发明涉及一种仿酶催化氧化断裂叔胺C-N键的方法，属于化学与工程技术领域。
背景技术
C-N键作为常见的化学键广泛分布在有机分子中，其活化与断裂一直是有机化学、有机金属化学和生物化学中的研究热点。例如蛋白质与氨基酸之间的相互转化离不开C-N键的形成与断裂，对人体生命活动具有重要作用。国内外对于C-N键构建研究较多，方法比较成熟。而由于氮原子含有孤对电子，电子云密度较大，C-N键的键长较短，不易被极化，反应活性较低，含氮基团较难离去，断裂C-N键是有机合成中的一大难题。目前对于C-N键断裂的研究主要集中于氧化断裂C-N键，包括过渡金属催化、强氧化剂氧化、光催化、生物酶催化等途径，寻找绿色、高效、适用性广的断裂途径一直是研究热点。
P450单加氧酶是一个具有催化氧化反应的酶家族，广泛存在于自然界动植物、微生物体内，在生物体内具有调节脂溶性维生素，药物代谢等功能。被报道用于多种反应，如杂原子脱烷基、硫氧化、酰胺及半缩醛的形成、C-H羟基化、C-H氨基化等。虽然酶催化具有作用温和、选择性高的优势，但也限制了其在更广泛条件下的应用，而且大部分P450酶依赖昂贵的NADPH等辅酶发挥作用，这些都限制了其实际规模化应用。P450酶的活性中心是明确的以Fe为金属中心的卟啉结构，科研工作者以此为启发，将目标转向了仿酶体系。仿P450酶金属卟啉催化剂已经被报道用于甲苯，乙苯，环己烷等饱和C-H键的氧化，烯烃氧化以及环氧化等反应。因此，从催化氧化的角度，设计廉价金属为活性中心，利用卟啉取代基调控催化剂活性，以氧气为氧化剂，有望建立一种绿色、高效的仿酶催化断裂叔胺C-N键的新方法。
发明内容
本发明针对现有叔胺C-N键断裂困难、反应条件苛刻的问题，提供一类P450酶来源的仿酶催化剂，于温和条件断裂叔胺C-N键的新方法。
本发明的技术方案：
本发明的目的之一是提供一种仿酶催化氧化断裂叔胺C-N键的方法，该方法具体为：将叔胺底物溶于溶剂中，并将催化剂、助催化剂、氧化剂加入反应体系中，加热反应，得到仲胺产物。
进一步限定，叔胺底物为N-苄基修饰的叔胺化合物。
更进一步限定，叔胺底物为1-苄基哌啶、1-苄基吗啉、1-苄基-四氢吡咯、9-苄基咔唑或N,N-二甲基苄胺。
进一步限定，溶剂为二甲亚砜、丙酮、乙腈、氯仿、二氯甲烷、N,N-二甲基甲酰胺、四氢呋喃、水中一种或几种混合。
进一步限定，溶剂与叔胺底物的体积质量比为5mL：(0.05～0.15)g。
进一步限定，仿酶催化剂为卟啉的金属络合物，结构如下：
式中，X为-Br、-Cl、-OCF3、-F、-OCH3、-OPh、-H、-COOCH3、-CF3；M为Fe2+或Mn2+。
进一步限定，助催化剂为N-羟基邻苯二甲酰亚胺(NHPI)、N,N’-二羟基均苯四甲酸二胺(NDHPI)、2,2,6,6-四甲基哌啶-氮-氧化物(TEMPO)中的一种或几种混合。
进一步限定，氧化剂为过氧化氢、氧气、间氯过氧苯甲酸、过氧苯甲酸叔丁酯、2-碘酰基苯甲酸中的一种或几种混合。
进一步限定，催化剂、助催化剂、氧化剂和底物的物质的量之比(0.001～0.010)：(0.01～0.25)：(0.02～2)：1。
进一步限定，反应温度为40～100℃，时间为1～48h。
进一步限定，仲胺产物为咔唑。
进一步限定，反应结束后取反应液10uL加入到990uL乙腈中，然后使用有机滤膜去除不溶物，得到稀释100倍的待检测产率样品。
本发明提供了利用仿酶催化剂催化叔胺C-N键断裂的方法，具体将芳基叔胺类底物加入溶剂后，分别加入Fe卟啉类仿酶催化剂、助催化剂、氧化剂，升温反应断裂C-N键，生成苯甲醛等芳基脱出副产物与仲胺产物，实现C-N键选择性断裂，解决了现有断裂叔胺C-N键困难，反应条件苛刻的问题。与现有技术相比，本发明具有以下有益效果：
(1)本发明选取芳基叔胺类化合物为原料，利用廉价金属Fe、Mn为卟啉活性中心，转化氧气为过氧结构与四价Fe、Mn的络合物；利用NHPI等助催化剂活化底物N-亚甲基为自由基；二者协同作用下生成苯甲醛等苄基氧化产物，实现C-N键的选择性断裂，生成咔唑等仲胺产物。
(2)本发明利用催化氧化体系，采用绿色的氧气、过氧化氢等氧化剂即可实现C-N键断裂，无需高锰酸钾等传统氧化剂，且催化效率是其7倍以上，具有绿色高效的特点。
附图说明
图1为仿酶催化剂的化学结构示意图；
图2为原料9-苄基咔唑的液质检测结果；
图3为实施例4得到的反应液的液质检测结果(M+H+＝168)
图4为咔唑标品的液相检测结果(保留时间为5.118min)；
图5为实施例4得到的反应液的液相检测结果(保留时间为5.170min)。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书实施例对本发明的具体实施方式做详细的说明。
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。
实施例1
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入二氯甲烷(5mL)。
步骤2：称取Fe-PP-OCF3(1mg，0.001mmol)、NHPI(15mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至40℃，反应24h后中止反应。
Fe-PP-OCF3制备方法：
将吡咯(0.067mol)和对甲氧基苯甲醛(0.067mol)混合于丙酸(200mL)中回流10h，然后将反应液冷却至室温。将沉淀过滤后，用甲醇与乙酸乙酯的混合溶液(v：v＝4：1)洗涤，然后在烘箱中干燥，得PP-OCF3。
称取PP-OCF3(1mmol)、FeCl2·4H2O(12.8mmol)，混合于DMF(100mL)中，加热回流6h。反应液冷却至室温，加入蒸馏水(150mL)，将沉淀过滤，用蒸馏水(50mL)洗涤两次，沉淀溶于三氯甲烷，用1M HCl洗1次，水洗2次，有机层用无水MgSO4干燥，蒸干得Fe-PP-OCF3。
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为5.5％。
对比例1：
0℃条件下于20mL瓶中加入9-苄基咔唑(129mg，0.5mmol)，四乙基溴化铵(116.5mg，0.555mmol)，溶于二氯甲烷(10mL)，将高锰酸钾(158mg，1mmol)与无水碳酸钠(50mg)分六批加入(每隔10min加入一批，1h加完)，40℃反应24h，液相测定咔唑产率为0.7％。
对比实施例1和对比例1的数据可知，仿酶催化剂Fe-PP-OCF3催化下的C-N键断裂体系，能够有效提高C-N键断裂产物咔唑的产率，具有催化叔胺C-N键断裂活性。
实施例2：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)。
步骤2：称取Fe-PP-OCF3(1mg，0.001mmol)、NHPI(15mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至40℃，反应24h后中止反应。
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为7.9％。
实施例3：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)；
步骤2：称取Fe-PP-OCF3(1mg，0.001mmol)、NHPI(15mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至60℃，反应24h后中止反应
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为14.7％。
实施例4：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)；
步骤2：称取Fe-PP-OCF3(1mg，0.001mmol)、NDHPI(22mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至60℃，反应24h后中止反应
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为19.1％。
本实施例反应液液质检测结果和液相检测结果如图3和图5所示，咔唑标品的液相检测结果如图4所示，原料9-苄基咔唑的液质检测结果如图2所示。
实施例5：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)。
步骤2：称取Fe-PP-F(0.74mg，0.001mmol)、NDHPI(22mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至60℃，反应24h后中止反应。
Fe-PP-F制备方法：
将吡咯(0.067mol)和对氟苯甲醛(0.067mol)混合于丙酸(200mL)中回流10h，然后将反应液冷却至室温。将沉淀过滤后，用甲醇与乙酸乙酯的混合溶液(v：v＝4：1)洗涤，然后在烘箱中干燥，得PP-F。
称取PP-OCF3(1mmol)、FeCl2·4H2O(12.8mmol)，混合于DMF(100mL)中，加热回流6h。反应液冷却至室温，加入蒸馏水(150mL)，将沉淀过滤，用蒸馏水(50mL)洗涤两次，沉淀溶于三氯甲烷，用1M HCl洗1次，水洗2次，有机层用无水MgSO4干燥，蒸干得Fe-PP-F。
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为19.8％。
实施例6：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入二氯乙烷(5mL)；
步骤2：称取Fe-PP-F(0.74mg，0.001mmol)、NHPI(15mg，0.09mmol)、30％过氧化氢溶液(113mg，1mmol)，升高反应温度至80℃，反应24h后中止反应
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为22.4％。
实施例7：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)；
步骤2：称取Fe-PP-F(0.74mg，0.001mmol)、TEMPO(15mg，0.09mmol)、过氧苯甲酸叔丁酯(194mg，1mmol)，升高反应温度至60℃，反应24h后中止反应
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为15.2％。
实施例8：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)。
步骤2：称取Fe-PP-OPh(1mg，0.001mmol)、NHPI(15mg，0.09mmol)、30％过氧化氢溶液(113mg，1mmol)，升高反应温度至60℃，反应24h后中止反应。
Fe-PP-OPh制备方法：
将吡咯(0.067mol)和对苯氧基苯甲醛(0.067mol)混合于丙酸(200mL)中回流10h，然后将反应液冷却至室温。将沉淀过滤后，用甲醇与乙酸乙酯的混合溶液(v：v＝4：1)洗涤，然后在烘箱中干燥，得PP-OPh。
称取PP-OCF3(1mmol)、FeCl2·4H2O(12.8mmol)，混合于DMF(100mL)中，加热回流6h。反应液冷却至室温，加入蒸馏水(150mL)，将沉淀过滤，用蒸馏水(50mL)洗涤两次，沉淀溶于三氯甲烷，用1M HCl洗1次，水洗2次，有机层用无水MgSO4干燥，蒸干得Fe-PP-OCF3。
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为17.2％。
实施例9：
步骤1：室温搅拌条件下，于25mL茄形瓶中，加入9-苄基咔唑(129mg，0.5mmol)，加入三氯甲烷(5mL)；
步骤2：称取Fe-PP-OPh(1mg，0.001mmol)、NHPI(15mg，0.09mmol)，过氧苯甲酸叔丁酯(97mg，0.5mmol)，氧气球条件下，升高反应温度至60℃，反应24h后中止反应
步骤3：取10uL反应液稀释至990uL乙腈中，通过有机滤膜去除不溶物，液相测定咔唑产率为20.2％。
虽然本发明已以较佳的实施例公开如上，但其并非用以限定本发明，任何熟悉此技术的人，在不脱离本发明精神和范围内，都可以做各种的改动与修饰，因此，本发明的保护范围应该以权利要求书所界定的为准。
Claims (10)
1.一种仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，将叔胺底物溶于溶剂中，并将催化剂、助催化剂、氧化剂加入反应体系中，加热反应，得到仲胺产物。
2.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，叔胺底物为N-苄基修饰的叔胺化合物，具体的为1-苄基哌啶、1-苄基吗啉、1-苄基-四氢吡咯、9-苄基咔唑或N,N-二甲基苄胺。
3.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，溶剂为二甲亚砜、丙酮、乙腈、氯仿、二氯甲烷、N,N-二甲基甲酰胺、四氢呋喃、水中一种或几种混合。
4.根据权利要求1或3所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，溶剂与叔胺底物的体积质量比为5mL：(0.05～0.15)g。
5.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，仿酶催化剂为卟啉的金属络合物，结构如下：
式中，X为-Br、-Cl、-OCF3、-F、-OCH3、-OPh、-H、-COOCH3、-CF3；M为Fe2+或Mn2+。
6.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，助催化剂为NHPI、NDHPI、TEMPO中的一种或几种混合。
7.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，氧化剂为过氧化氢、氧气、间氯过氧苯甲酸、过氧苯甲酸叔丁酯、2-碘酰基苯甲酸中的一种或几种混合。
8.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，催化剂、助催化剂、氧化剂和底物的物质的量之比(0.001～0.010)：(0.01～0.25)：(0.02～2)：1。
9.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，反应温度为40～100℃，时间为1～48h。
10.根据权利要求1所述的仿酶催化氧化断裂叔胺C-N键的方法，其特征在于，仲胺产物为咔唑。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5141911A (en) * | 1989-08-10 | 1992-08-25 | Societe Nationale Elf Aquitaine | Oxidation catalysts based on supported metalloporphyrin |
| US20140228561A1 (en) * | 2011-09-21 | 2014-08-14 | National University Corporation Okayama University | Metalloporphyrin complex, manufacturing process therefor and carbon dioxide fixation catalyst therefrom, as well as process for manufacturing cyclic carbonate |
| CN108484504A (zh) * | 2018-04-28 | 2018-09-04 | 中国科学院青岛生物能源与过程研究所 | 一种仿生催化断裂芳基含氮化合物中c-n键的方法 |
-
2023
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5141911A (en) * | 1989-08-10 | 1992-08-25 | Societe Nationale Elf Aquitaine | Oxidation catalysts based on supported metalloporphyrin |
| US20140228561A1 (en) * | 2011-09-21 | 2014-08-14 | National University Corporation Okayama University | Metalloporphyrin complex, manufacturing process therefor and carbon dioxide fixation catalyst therefrom, as well as process for manufacturing cyclic carbonate |
| CN108484504A (zh) * | 2018-04-28 | 2018-09-04 | 中国科学院青岛生物能源与过程研究所 | 一种仿生催化断裂芳基含氮化合物中c-n键的方法 |
Non-Patent Citations (3)
| Title |
|---|
| NAOKI MIYATA, ET AL.: ""Oxidative Dealkylation of Tertiary Amines by Iron(III) Porphyrin-Iodosoxylene System as a Model of Cytochrome P-450"", 《CHEM.PHARM.BULL.》, vol. 29, no. 5, 31 December 1981 (1981-12-31), pages 1489 - 1492 * |
| 徐保明等: ""含氮化合物在甲苯氧化中的应用进展"", 《应用化工》, vol. 47, no. 3, 31 March 2018 (2018-03-31), pages 580 - 583 * |
| 谭志伟: ""共轭金属卟啉聚合物与N-羟基邻苯二甲酰胺的共催化研究"", 《中国优秀硕士学位论文全文数据库 工程科技I辑》, no. 7, 15 July 2018 (2018-07-15), pages 014 - 530 * |
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