Luận án TS: Flo, CF3 hóa hợp chất hữu cơ bằng xúc tác dị thể - Nguyễn Văn Tú

VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY HO CHI MINH UNIVERSITY OF TECHNOLOGY ----&&*&&---- NGUYӈ19Ă17Ò INTRODUCING FLUORINE AND TRIFLUOROMETHYL GROUP INTO ORGANIC COMPOUNDS UNDER HETEROGENEOUS TRANSITION METAL CATALYSIS PhD THESIS HO CHI MINH CITY, 2018 VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY HO CHI MINH UNIVERSITY OF TECHNOLOGY ----&&*&&---- NGUYӈ19Ă17Ò INTRODUCING FLUORINE AND TRIFLUOROMETHYL GROUP INTO ORGANIC COMPOUNDS UNDER HETEROGENEOUS TRANSITION METAL CATALYSIS Major: Chemical Engineering Major code: 62.01 Independent Reviewer No.1: 3URI'UĈLQK7Kӏ Ngӑ Independent Reviewer No. Phҥm NguyӉn Kim TuyӃn Reviewer No. NguyӉQ3KѭѫQJ7QJ Reviewer No. NguyӉn Thӏ Dung Reviewer No.

Bҥch Long Giang ADVISORS: 1. 3KDQ7KDQK6ѫQ1DP 2. 7UѭѫQJ9NJ7KDQK DECLARATION OF ORIGINALITY I hereby declare that this thesis represents my original work under the advice from Dr. 7UѭѫQJ9NJ7KDQK and Prof.

'U3KDQ7KDQK6ѫQ1DP, and that all figures and results obtained in this thesis are absolutely true and have been not yet released ever before. All data, tables, figures and text citations which have been reproduced from any other source, including the internet, have been explicitly acknowledged as such. I am aware that in case of non-compliance, I have to be under any judgement from the scientific committee. Ho Chi Minh City, 2018 Performer NguyӉQ9ăQ7~ i TÓM TҲT LUҰN ÁN Các hӧp chҩt chӭa mӝt hay nhiӅu nguyên tӱ flo trong phân tӱ có nhӳng tính chҩWÿһc biӋt ÿѭӧc hình thành bӣLNtFKWKѭӟc nhӓ Yjÿӝ kPÿLӋn cao cӫa flo.

Sӵ có mһt cӫa flo trong phân tӱ hӧp chҩt làm WăQJÿӝ kPÿLӋQWtQKѭDPӥÿӝ әQÿӏnh sinh hӑc các hӧp chҩt chӭa nó Yjÿһc biӋt là WăQJ hoҥt tính sinh hӑc cӫa chúng. Do vұy, các hӧp chҩt chӭDIORÿѭӧc sӱ dөng ngày càng nhiӅXWURQJKyDQ{QJKyDGѭӧc và trong nhiӅu loҥi vұt liӋu. Ngoài ra, các hӧp chҩt chӭDÿӗng vӏ flo 18 (18F) FzQÿѭӧc sӱ dөng rӝng rãi trong kӻ thuұt Positron Emission Tomography (PET) ӭng dөng trong y hӑc. Chính vì vұy, nhiӅu công trình nghiên cӭXÿmÿѭӧc các nhà khoa hӑc trên thӃ giӟi thӵc hiӋQÿӇ WuPUDFiFSKѭѫQJSKiSNKiFQKDXWәng hӧp các hӧp chҩt chӭa flo7X\QKLrQGRÿһc ÿLӇm hoҥt tính hóa hӑc mҥnh cӫa flo mà các phҧn ӭng tәng hӧp ÿӅu có nhӳQJQKѭӧc ÿLӇPQKѭVLQKUDQKLӅu sҧn phҭm phө, ÿLӅu kiӋn phҧn ӭng khҳc nghiӋt, sӱ dөng các chҩt phҧn ӭQJYj[~FWiFÿҳt tiӅn hoһc phҥm vi chҩt nӅn hҽSYY+ѫQQӳa, tҩt cҧ các phҧn ӭQJWURQJOƭQKYӵc hóa hӑFIORÿmÿѭӧc công bӕ WUѭӟFÿk\ ÿӅu sӱ dөng kim loҥi chuyӇn tiӃp làm xúc tác ÿӗng thӇ hoһc ÿѭӧc sӱ dөQJQKѭ chҩt phө trӧ trong hӋ ÿӗng thӇ, FKѭD Fy F{QJ WUuQK QJKLrQ FӭX QjR ÿѭӧc thӵc hiӋn WURQJ ÿy sӱ dөng kim loҥi chuyӇn tiӃp làm chҩt xúc tác dӏ thӇ, góp phҫn vào viӋFWăQJNKҧ QăQJWiLVӱ dөng và tiӃt kiӋm chi phí (dӵa trên tìm hiӇu cӫa nhóm nghiên cӭu và tìm kiӃm trên SciFinder WtQKÿӃQWKiQJQăP).

Vӟi sӵ phát triӇn mҥnh mӁ tӯ nhӳng ӭng dөng cӫa hӧp chҩt hӳXFѫNLPORҥi MOFs và hҥWQDQR QDQRSDUWLFOHV FK~QJW{LÿmQJKLrQFӭu tәng hӧp và sӱ dөng MOFs Cu(INA)2 và hҥt nano delafossite AgFeO2 làm xúc tác cho phҧn ӭng gҳn nhóm -CF3 (trifluoromethylation) và gҳn flo (fluorination) - nhӳng phҧn ӭng ÿѭӧc nghiên cӭu phә biӃn hiӋn nay. KӃt quҧ khҷQJÿӏnh sӵ tәng hӧp thành công cӫa MOFs Cu(INA)2 và hҥt nano AgFeO2 vӟi nhӳQJÿһc tính trùng khӟp vӟi các nghiên cӭXWUѭӟc. ViӋc sӱ dөng chúng vào các phҧn ӭng flo KyDÿmPDQJOҥi nhӳng kӃt quҧ QJRjLPRQJÿӧLÿѭӧc thӇ hiӋn ӣ hiӋu suҩt phҧn ӭQJFKRÿDVӕ các chҩt nӅn khác nhau cho kӃt quҧ cao và rҩWFDR+ѫQQӳa, các xúc tác sӱ dөQJÿѭӧc thu hӗi và sӱ dөng lҥi nhiӅu lҫn mà không có sӵ giҧPÿiQJNӇ hiӋu suҩt phҧn ӭng FNJQJQKѭVӵ phá vӥ cҩu trúc tinh thӇ cӫa xúc tác. Nhӳng kӃt quҧ trên ÿm khҷQJÿӏnh sӵ thành công cӫDÿӅ tài nghiên cӭu sӱ dөng xúc tác dӏ thӇ tâm kim loҥi chuyӇn tiӃp WURQJOƭQKYӵc hóa hӑc flo.

ii ABSTRACT There have not been recorded articles yet, conducting the fluorination of boronic acids and aliphatic acids under the heterogeneous catalysis (according to searching on SciFinder and under our consideration till August 2018). Due to the precious characteristics of fluorinated compounds in the human life, especially in biochemistry, several studies have been investigated to find out different methods for fluorinating organic compounds. In spite of the increasing developments in fluorine chemistry, the drawbacks have still remained. The use of strong reagents leading to the generation of several isomers, the use of expensive reagents resulting in the enhanced expense, the application of harsh conditions and the limited substrate scope have been the major disadvantages so far.

Therefore, the novel methods for the transformation of organic frameworks into fluorinated ones are needed. Herein, we developed the first heterogeneous catalyzed fluorination of aliphatic acids and the first heterogeneous catalyzed trifluoromethylation of boronic acids using the successfully synthetic catalysts of Cu(INA)2 MOFs and AgFeO2 nanoparticles. The characterization of the two mentioned catalysts proved the similarity to the previous materials described in the former studies. They were employed in the fluorination and trifluoromethylation reactions.

Interestingly, they exhibited the unexpected compatibility with the fluorination reactions with the high to excellent yields of the desired products and the wide substrate scope. They also showed the high recoverability and reusability as they were recovered and reused several times without significant degradation in product yields. The leaching tests showed the stable crystallinity of above catalysts in the reaction mixtures, wherein no enhanced yield was observed by the contribution of leached active species, if any. The results from our developments proved the success in the syntheses of catalyst materials as well as in the fluorination reaction of aliphatic acids and trifluoromethylation of boronic acids under the mild, efficient conditions.

Our studies will contribute to the fluorine chemistry the novel methods for the fluorination and trifluoromethylation described in this thesis. And futher studies will focus on using various transition metal catalysts for fluorinating different organic compounds. iii ACKNOWLEDGEMENT First and foremost, I want to send my deep thanks to my advisors namely Doctor Thanh Truong and Prof Nam T. Phan for the thorough, thoughtful guidance with their comprehensive knowledge and their financial support, contributing to the success of this thesis.

Working with them is my honor, and I have gained much precious experience for my future work. I also give thanks for the considerate help to teachers in Department of Organic Chemical Engineering and all staffs in the MANAR Lab, who always have given me any aids when needed. Additionally, I want to give thanks to my research group including Mr. for the valuable support, which helps me complete this thesis.

Last but not least, I want to express my limitless gratefulness to all members in my family who have been always beside me in the hardest time. Their encouragement and support inspire me the strength and belief in my study and my life. Ho Chi Minh City, 2018 NguyӉQ9ăQ7~ iv TABLE OF CONTENTS DECLARATION OF ORIGINALITY. iv TABLE OF CONTENTS.

v LIST OF FIGURES.viii LIST OF SCHEMES. x LIST OF TABLES .xiii LIST OF ABBREVIATIONS. 1 Chapter 1 : LITERATURE REVIEW. Introduction of fluorine into organic scaffolds.

Introduction of trifluoromethyl group (CF3 group) into organic compounds. Metal organic frameworks (MOFs), delafossite-type oxides and nanoparticles in organic syntheses. MOFs in organic chemistry. Silver-Ferrite Nanoparticles AgFeO2.

Aim and objectives. Materials and instrumentation. Preparation of metal organic framework Cu(INA)2. Preparation of Delafossite-type oxide AgFeO2 nanoparticles.

Copper-catalyzed trifluoromethylation of aryl boronic acids using MOFs Cu(INA)2 as catalyst (reaction 1). Determination of GC yield. Silver-catalyzed fluorination of aliphatic acids using AgFeO2 as catalyst (reaction 2). Determination of GC yield.

49 Chapter 3 : RESULTS AND DISCUSSION. Catalyst synthesis and characterization of Cu(INA)2. Characterization of Delafossite-type oxide AgFeO2 (silver-ferrite oxide). Copper-catalyzed trifluoromethylation of aryl boronic acids using MOFs Cu(INA)2 as catalyst.

Effect of catalyst loading on reaction yield. Effect of fluoride anion sources on reaction yield. Effect of temperature on reaction yield. Effect of reactant molar ratio on reaction yield.

Effect of ligand amount on reaction yield. Effect of solvent on reaction yield. Effect of reaction environment and oxidant on reaction yield. Reaction with different copper-based catalysts.

Catalyst recycling studies. Substrate scope studies. Silver-catalyzed fluorination of aliphatic acids using AgFeO2 as catalyst. Effect of SelectFluor equivalent on reaction yield.

Effect of catalyst loading on reaction yield. Effect of different solvents on reaction yield. Effect of volume ratio of acetone to water on reaction yield. Effect of the concentration of reactant on reaction yield.

Effect of temperature on reaction yield. Reaction with different silver- and other metals-based catalysts. Catalyst recycling studies. Substrate scope studies.

Initial study for the feasible pathway of the reaction. 99 LIST OF PUBLICATIONS. 117 vii LIST OF FIGURES Figure 1. Some popular drugs containing fluorines [9].

Naturally occuring fluorinated compounds [10]. Some common N-fluoro reagent classes as fluorine sources [14-17]. Some nucleophilic fluorinating reagents used in fluorination reactions [5]. Hypervalent iodine perfluoroalkyl reagents [63-67].

Different forms of Yagupolski-Umemoto reagents used in trifluoromethylation of organic compounds [65]. View of the crystal structure of Cu(INA)2 [147]. Delafossite-type crystal structure of AgFeO2. Unit-cell of (a) 3R polytype and (b) 2H polytype [159].

Calibration curve for determining GC yield of 4-trifluoromethyl anisole. Calibration curve for determining GC yield of (2-fluoroethane-1,1- diyl)dibenzene. XRD patterns of (a) the synthesized Cu(INA)2;. FT±IR spectra of the Cu(INA)2 (a) and isonicotinic acid HINA (b).

SEM micrograph of the Cu(INA)2. TGA result of the Cu(INA)2. XRD patterns of the synthesized AgFeO2 (a);. SEM and TEM images of AgFeO2 nanoparticles.

TGA profile of AgFeO2 nanoparticles. Effect of catalyst loading on reaction yield. Effect of fluoride ion sources on reaction yield. Reaction yields at different temperature.

The reaction yields under various equivalent of TMSCF3. Reaction yields obtained under various amount of 1,10-phenanthroline. Catalyst recycling studies. FT-IR spectra of the fresh (a) and reused (b) Cu(INA)2 catalyst.

X-ray powder diffractograms of the fresh (a) and reused (b) Cu(INA)2 catalyst. Reaction yields with different amount of SelectFluor as fluorine reagent. Effect of various catalyst loadings of AgFeO2 on reaction yield. Reaction yields obtained with different solvents.

The effect of volume ratio of acetone to water on reaction yield. Reaction yields under various concentrations of reactant. Reaction yields obtained at various temperature. Catalyst recycling studies.

The XRD spectra of (a) the fresh AgFeO2 and (b) the recovered AgFeO2. 92 ix LIST OF SCHEMES Scheme 1. Electrophilic fluorination of aryl boronic acids and trifluoroborates [18]. Fluorination of aryl Grignard reagents [19-21].

Transition metal catalyzed fluorinations with directing groups [22, 23]. Fluorination of aryl stannanes, boronic acids and silanes [24-26]. Pd-catalyzed Aminofluorination of Unactivated Alkenes [27, 28]. Two steps for fluorination of ketones with N-fluoro reagent of SelectFluor [34].

Fluorination of ketones with N-fluoro reagent SelectFluor [35]. Transition metal catalyst for aliphatic C-F bond formation [22]. Fluorination of carboxylic acids using fluorine as reagent [38]. Nucleophilic fluorination using DAST as fluorinating reagent [39].

The aryl fluoride formation via palladium-catalyzed fluorination [40]. Copper-catalyzed aryl-F formation with AgF [42]. Fluorination of Aryl Iodides with (tBuCN)2CuOTf and AgF [43]. The C-F bond formation from cyclic allylic chlorides using Pd(0) as catalyst [44].

Iridium-catalyzed fluorination of organic halides [45]. Manganese catalyzed nucleophilic fluorination of C(sp3)-H bond [46] 15 Scheme 1. The radical fluorination pathway [47]. The fluorodecarboxylation of aliphatic acids under XeF2 [50-53].

Photo-fluorodecarboxylation of 2-aryloxy and 2-aryl carboxylic acids [55]. Radical mechanism of photo-decarboxylation of carboxylic acids [55] 17 Scheme 1. Fluorodecarboxylation of aliphatic acids with silver as catalyst [56]. Three pathways hypothesized for the formation of alkyl radical [57].

The difference between methyl group and trifluoromethyl group [58-60]. Route via fluoroalkylcopper intermediate by McLoughlin and Thrower [62]. 20 6FKHPH5HDFWLYLW\RIDOFRKRO7RJQL¶VUHDJHQWYLDYDULRXVH[DPSOHV>@. The low yields in trifluoromethylation of phenols using reagent 2 [73] 23 Scheme 1.