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doi.org/10.26434/chemrxiv.13213517.v1

Visible-Light-Induced Deep Aerobic Oxidation of Alkyl Aromaticschangchengwang wang, guoxiang zhang, zhiwei zuo, rong zeng, dandan zhai, Feng Liu, Zhangjie Shi

Submitted date: 18/01/2021 • Posted date: 19/01/2021Licence: CC BY-NC 4.0Citation information: wang, changchengwang; zhang, guoxiang; zuo, zhiwei; zeng, rong; zhai, dandan; Liu,Feng; et al. (2021): Visible-Light-Induced Deep Aerobic Oxidation of Alkyl Aromatics. ChemRxiv. Preprint.https://doi.org/10.26434/chemrxiv.13213517.v1

Oxidation is a major chemical process to produce oxygenated chemicals in both nature and chemical industry.Currently, industrial deep oxidation processes from polyalkyl benzene are major routes to produce benzoicacids and benzene polycarboxylic acids (BPCAs), while to some extent suffering from the energy-intensiveand potentially hazardous drawbacks and the sluggish separation issues. In this report, visible-light-induceddeep aerobic oxidation of (poly)alkyl benzene to benzene (poly)carboxylic acids was developed. CeCl3 wasproved to be an efficient HAT (Hydrogen Atom Transfer)catalyst in the presence of alcohol as both hydrogenand electron shuttle. Dioxygen (O2) was found as a sole terminal oxidant. In most cases, pure products wereeasily isolated by simple filtration, showing the advantages of for scaling up. The reaction provides an idealway to form valuable fine chemicals from abundant petroleum feedstocks.

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Article

Visible-Light-Induced Deep Aerobic Oxidation of Alkyl Aromatics Chang-Cheng Wang1, Guo-Xiang Zhang2, Zhi-Wei Zuo3*, Rong Zeng2, Dan-Dan Zhai1, Feng Liu1* and Zhang-Jie Shi1,3*.1Department of Chemistry, Fudan University. Shanghai, 200438, China. 2Department of Chemistry, School of Science, Xi’an Key Laboratory of Sustainable Energy Materials Chemistry, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China. 3State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. 4State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry. Shanghai, 200032, China. ABSTRACT: Oxidation is a major chemical process to produce oxygenated chemicals in both nature and the chemical industry. Currently, industrial deep oxidation processes from polyalkyl benzene are primary routes to produce benzoic acids and benzene polycarboxylic acids (BPCAs), while to some extent suffering from the energy-intensive and potentially hazardous drawbacks and the sluggish separation issues. In this report, visible-light-induced deep aerobic oxidation of (poly)alkyl benzene to benzene (poly)carboxylic acids was developed. CeCl3 was proved to be an efficient HAT (Hydrogen Atom Transfer)catalyst in the presence of alcohol as both hydrogen and electron shuttle. Dioxygen (O2) was found as a sole terminal oxidant. In most cases, pure products were easily isolated by simple filtration, showing the advantages of scaling up. The reaction provides an ideal way to form valuable fine chemicals from abundant petroleum feedstocks.

Benzene polycarboxylic acids (BPCAs) are key intermediates in the preparations of resins, plasticizers, pharmaceutical acids, food preservatives, as well as the modulator in the synthesis of Metal-Organic Frameworks (MOF) 1-6. Terephthalic acid (TPA), for example, be consumed principally as a monomer precursor in the manufacture of polyester (PET), has become one of the most in-demand chemicals with an annual output of up to a hundred million tons7. Benzoic acid, with million tons annually production, is commonly used as a pH adjustor, food preservation, and valuable starting material in the chemical industry8. Functionalized benzoic acids are also widely spread in drug discovery, material chemistry, agrochemicals as starting materials and critical ingredients. Salicylic acid itself is a druggable molecule and is mostly used in personal care, food & preservatives. Mefenamic acid is known as a nonsteroidal anti-inflammatory drug (NSAID), which has beenused for short-term pain relief treatment and blood loss from menstrual periods (Fig.1a). BPCAs are chemically synthesized through a series of oxidation reactions from the corresponding alkyl aromatics. The most notable commercial process, known as the Amoco process9, employs liquid-phase aerobic oxidation with homogeneous Co-Mn-Br catalyst system in acetic acid medium9-11. These processes

commonly accompany high energy consumption at high temperatures (175-225 oC) and high dioxygen pressure (15-30 atm). The use of transition metal bromides12 leads to a potential hazard to the environment and stratospheric ozone. Indeed, several severe safety accidents were caused by this point in the past few years, which has triggered public panic and protest (Fig.1b)13. Other developed approaches in direct oxidations of alkyl aromatics include the following ways: i) stoichiometric oxidation by using highly reactive inorganic and/or organic oxidants (KMnO4, iodineV species, t-BuOOH, m-CPBA, H2O2, NHPI, etc.)14-20; ii) catalytic aerobic oxidation catalyzed by heterogeneous catalysts (e.g., polymer- or montmorillonite clay-supported catalysts, Pd, Au, or Co nanoparticles) (Fig.1b)10,21-24. The former processes suffered from the requirement of stoichiometric amounts of harmful or unsafe oxidants. The drawbacks of the latter protocols can be ascribed to some common disadvantages of heterogeneous catalysts, including the leaching problems of catalysts, limited oxidation efficiency and/or selectivity. Chemists never stop searching for a clean and efficient way for the catalytic oxidation of alkyl aromatics to BCPAs ,to meet the green and sustainable requirements in industry.

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Article

COOH

COOH

COOH

b)

a)

R1

[Ox] = KMnO4, iodine(V), t-BuOOH m-CPBA, H2O2, NHPI, etc.

d)

or Heterogeneous Catalysts

c)

COOH

p-toloyl acid

O2Sunlight

on the roof

1 year

COOH

COOH

terephthalic acid (TPA)

TPA, 100 million ton/abenzoic acid1 million ton/a

COOHOH

salicylic acid

NHCOOH

Mefenamic acid

Homogeneous Oxidation

PX

COOH

COOHTPA

Amoco process COOH

+

PX

COOH

COOH

TPAPX

CeCl3O2 ROH

Fig.1| The nature of benzene (poly)carboxylic acids. a, Aromatic (poly)carboxylic acid-related products in daily life. b, Traditional oxidation of alkylbenzene. c, Photochemistry on the roof: The first oxidation of alkyl aromatics with molecular oxygen explored by Ciamician and Silber 100 years ago. d, Visible-light-induced deep aerobic oxidation of (poly)alkyl aromatics to aromatic (poly)carboxylic acids.

Ciamician and Silber reported the first photo-induced oxidation of alkyl aromatics with molecular oxygen in 191225. Authors exposed toluene, o-xylene, m-xylene, p-xylene, and p-cymene to oxygen and sunlightfor about a year without any photosensitizer. The corresponding monocarboxylic acids were obtained as major products. Besides m- and p-toluyl acids, iso and terephthalic acids were also formed from m- and p-xylenes, respectively (Fig.1c). In recent years, photochemistry was re-announced, and photo-catalysts have been used to activate specific functional groups or substratesto complete various

transformations via energy or electron transfer. This typical application was proved as a safe and green synthesis protocol in organic synthesis26-33. Several elegant aerobic C-H bond photo-oxidation protocols were developed towards the synthesis of alcohol, aldehyde, and ketones in the past few decades34-39. Cerium salts were proved as efficient and favored photo-catalysts due to the relatively high abundance and excellent photo-catalytic performance. Zuo and co-workers developedsophisticated chemistry for the activation of C(sp3)-H bond through the synergistic utilization of hydrogen atom transfer (HAT) and ligand-to-metal charge

Article transfer process (LMCT) with Ce catalysts40-41. By the analysis of recent developments, we envisioned that via a photo-induced, Ce-promoted benzylic C(sp3)-H bond activation, the toluene derivatives could be deeply oxidized tocarboxylic acids in the presence of molecular oxygen as terminal oxidant through the radical pathway (Fig.1d). This approach might present novel, green and sustainable oxidation in both fundamental sciences and chemical industry toward valuable fine chemical productions from abundant feedstocks.

Results Reaction development. We set out to investigate the desirable photo-induced oxidation by examining 4-methyl-1,1'-biphenyl 3n as a prototypical substrate. After careful optimization, we established an efficient photo-oxidation protocol using CeCl3 (5 mol%) as a HAT catalyst in the presence of CCl3CH2OH (20 mol% for mono-methyl benzenes, 1.0 equiv. for polymethyl benzenes), irradiated by LED light under O2 (1 atm) in CH3CN for 24 h (see the supporting information for details.). The substrate scope was explored by oxidation of toluene and its derivatives. Benzoic acid 2a was obtained with 84% yield from toluene under standard conditions. The three xylenes 1b-1d were then irradiated with 40 w Kessil PR160L-390 nm light to give the corresponding phthalic acids in good yields. As to the oxidation of orthoxylene 1b, the in-situ formed phthalic acid will be spontaneously dehydrated to o-phthalic anhydride 2b. While trimethyl-, tetramethyl-, pentamethyl-, and even hexamethyl- benzenes (1e-1l) were introduced to the

developed catalytic photo-oxidation system, we were happy to find that all of these methyl groups were fully converted to benzene polycarboxylic acids (BPCAs, 2e-2l). By a simple work-up, all of these conversions were in good to excellent yields, showing the power of this oxidation protocol (Fig.2a). Due to the importance of BPCAs and the long-standing environmental and safety problems in their syntheses, this methodology provides a sustainable way to produce those basic chemicals that benefit for the human's livelihood and national economy. We then proceeded to test the scope of substituted toluene derivatives to extend the applications (Fig.2b). The oxidation of 2-methoxy- and 4-methoxy toluene underwent smoothly to give the corresponding benzoic acids 4a and 4b in 65% and 78% yield. A variety of para-substituted toluene substrates were then examined. Phenolic ester skeletons have recurred in many pharmaceutical molecules and natural products. The method makes it possible to proceed with the late-stage structure modification of those important molecules (4c-4e). Both electron-donating groups, like tert-butyl (4f), phenyl (4n), and electron-withdrawing groups CF3 (4g), NO2 (4h), COOEt (4l), CN (4m), as well as halogens (4i-4k) could tolerate this oxidation well, leaving useful synthetic functionalities for further derivatization. Meta-substituted toluene derivatives were oxidized to various benzoic acids (4o-4q), and slightly higher yields were given compared to their corresponding ortho- or para- isomers. Moreover, multi-substituted toluene derivatives were investigated, and all the oxidations worked well, showing good functional groups tolerance and synthetic diversity (4s-4x).

Article

2e 84%

2d 86%2b 65% 2c 85%

2f 59%

2k 69%

2h 75%

COOH

2a 84%

2i 79% 2l 49%2j 65%

2g 60%

a)

4a 65% 4e 68%4d 72%

4i 81% 4j 88% 4k 66% 4l 72%

4n 88%

4g 90%

4m 78%

4f 40%

4h 21%

4b 78%

4o 92%

4c 80%

4p 83%

4w 84%4s 87% 4v 78%4t 84% 4u 82% 4x 27%

CH3 COOHCOOH

COOH

OO

O

COOH

COOHCOOH

COOH

COOHCOOH

COOH

COOH

COOHHOOC

COOHCOOH

COOHCOOH

COOHCOOH

COOHHOOC

COOH

COOHHOOC

COOHCOOH

COOHHOOC

COOH

COOH

COOHHOOC

COOHHOOC

COOH

HOOC

COOHMeO

COOH COOH COOH COOH COOH

OMe OAc OCOiPr OBz tBu

COOH COOH COOH COOH COOH

CF3 NO2 F Cl Br

COOH

COOEt

COOH COOHCOOH COOH COOH

CN Ph

COOH

Ph F Cl

COOH COOHCOOH COOH COOH

Br Cl

COOH

Cl Cl COOMe F

CF3

F

Cl

Cl Br

F

F

F

4q 70% 4r 61%

b)

F

Fig.2| Deep areobic oxidation of (poly)methylbenzene. a, Oxidation of polyalkyl benzene 1 to BPCAs 2. b, Oxidation of substituted toluene 3 to substituted benzoic acids 4. Conditions: 1 or 3 (0.1 mmol), CeCl3 (5.0 mol%), CCl3CH2OH (20 mol% for mono-methyl benzenes, 1.0 equiv. for polymethyl benzenes) in CH3CN (2 mL) under 1 atm O2 atmosphere at 60 oC, and irradiated with a 400 nm/390 nm LED lamp for 24-72 h. See Supplementary Information for details.

Aromatic heterocyclic carboxylic acids widely existed in bio-active natural products, pharmaceutical compounds, and functional materials. Nevertheless, some could serve as multi-dentate ligands in coordination chemistry. We then introduced methyl heteroarenes to the developed oxidation system. To our delight, the oxidation reaction could proceed

smoothly, given the target aromatic heterocyclic carboxylic acids with the moderate to good yields (Fig.3a). Thiophene-2-carboxylic acid 6a, 5-acetyl thiophene-2-carboxylic acid 6b and benzo[b]thiophene-2-carboxylic acid 6c were obtained from the corresponding methyl- substrates 5a-5c. 4-Methyl pyridine 5e and even 3-methyl-1-phenyl-1H-

Article pyrazole 5f were compatible with this system, which could be converted to the heterocyclic carboxylic acid 6e-6f, albeit the latter with a lower efficacy. Substances with linear and branched alkyl substituents were then examined. We found that both benzylic C-H oxidation and C-C bond cleavage took place subsequently, delivering the corresponding carboxylic acid products in moderate yields (Fig.3b,3c). However, a benzylic C-H must be presented to initiate this oxidation process. It is important to note that when the mixture of toluene, ethylbenzene, cumene was introduced to this system, one sole benzoic acid product

2a was obtained with excellent yield (Fig.3d). This result illustrated that this oxidation reaction has a potent application in the separation and high-value transformation of the off-gases containing substituted benzene homologue compounds. Ultimately, this method was further applied to the late-stage modification of drugs. For example, the photocatalytic reaction of Celebrex, a non-steroidal anti-inflammatory drug, delivered the oxidized product 10 in 65% yield in one step (Fig.3e). Considering the importance of this kind of medicinal agent, we expect this methodology to be useful for drug modification by introducing hydrophilic carboxylic acid groups at a very late stage.

SCO2H

6c 74%

S CO2H

6b 81%

CO2HN

6d 71%

NN

6f 23% (NMR yield)6e 54% (60 h)

CO2HOSCO2H

6a 44%

b)

4k 60% 2d 77% 2d 41%

c)

NNF3C

SNH2

OO

Celebrex

e)

10

2a 83% 4n 76% 2a 84%

CO2H

CO2H

Ph

CO2H

NNF3C

CO2H

SNH2

OO

65%

N CO2H

Et n-Bu

CO2H CO2H

HO2C

CO2H

HO2C

HO2C

a)

Ph Br

Br

7a 7b 9a 9b 9c 9d

+

+

82%

1:1:1 mixture

d)

CO2H

1a

7a

9a

2a

Fig. 3| The substrate extension of the oxidation. a, Oxidation of the benzylic C-H bond in heterocyclic compounds. b, Secondary benzylic C-H oxidation

to benzoic acids through sequential cleavage of C-H and C-C bonds. c, Tertiary benzylic C-H oxidation. d, Oxidation of toluene, ethylbenzene, cumene

mixture. e, Late-stage diversification of medicinal reagent under standard reaction conditions.

To explore the mechanism of this catalytic oxidation , a series of control experiments were conducted (Fig. 4a). Firstly, a radical scavenger (TEMPO) was added under standard conditions, and no targeted product 4n was detected, indicating a possible radical pathway for this oxidation reaction .While attempting to capture the intermediates with TEMPO in the absence of O2, compound 11 was detected by GC-MS. This result provided reliable support of the existence of benzylic radicals, which might be the initiator of this photo-induced radical oxidative procedure. 18O2 was then used to take the place of O2, and undoubtedly only the

desired 18O labeled benzoic acid 4n’ was obtained with good yield, which clearly illustrated that the [O] atom in the product came from O2. To get more insight on the reaction mechanism, we carried out the oxidation of 3n with 1.0 eq. of CCl3CH2OH. The reaction was monitored by 1H NMR spectroscopy every 15 minutes (Fig.4b). Two key intermediates were traced during the reaction. The hydroperoxide was first observed, it was further oxidized after the peak at 45 min (12, green volcano l). Aldehyde was produced and get to its summit at around 90 mins (13, red

Article spot). Finally, both were transferred to the desired product (4n, blue triangle) at 135 minutes.

COOH

CH3CN, 60 o

C, 400 nm, O2

CeCl3 (5 mol%)

CCl3CH2OH (20 mol%)

18OH

18O

CH3CN, 60 o

C, 400 nm, 18O2

CeCl3 (5 mol%)

CCl3CH2OH (20 mol%)

HH

NOCH3CN, 60 oC, N2, 400 nm

CeCl3 (1.0 equiv.)

CCl3CH2OH (1.0 equiv.)

TEMPO (2.0 equiv.)

Ph

Ph Ph

Ph

11

3n 4n N.D.

3n

4n' 82%

3n

TEMPO (3.0 equiv.)

a)

- H+

R

O CCl3

O2 R

R O2R

O

OCl3C

CeIVCln

CeIIIClm

CeIVCln

O2

O2

H+

ROH

COOHH R

A B C

1 2

c)

D

R

R

visible light

R

R O2H

HAT

Ce, alcohol, O2

HO CCl3

SET Norrish type Ioxidation

R[O]

O2

Cl

OMe

SiMe3 SMe

78%

72%

76%

61%

82%COOH

Bpin

d)

2a

14

15

1617

18

Ph Ph

CHO+

O+

OH

12 13

4nCD3CN, 60

oC, O2

390 nm LED (40 W)

CeCl3 (5 mol%)

CCl3CH2OH (1 equiv.)3n

b)

Fig.4| Mechanistic investigations. a, Control experiments. b, Kinetic experiments. c, Plausible mechanism for the oxidation from toluene to benzoic acids. d, The deep oxidation of benzyl derivatives with heteroatom group substituents.

Based on the observations and previous studies, a plausible mechanism was proposed in Fig.4c. First, electrophilic alkoxy radical was generated from alcohol via Ce (IV)-alkoxide intermediate participated photo-induced LMCT process. Alkoxy radical then abstracted the hydrogen from benzylic C-H bond to form benzyl radical A; Subsequently, a single electron transfer occurred between molecular dioxygen (O2) and Ce(III) to form superoxide radical; The in-situ formed superoxide radical was involved in the reaction and oxidized the alkyl radicals to hydroperoxide B. After protonation and ROH released, D was obtained, which further accelerated the Norrish type I oxidation process to produce carboxylic acids 2 under illumination and heating conditions42. Under these reaction conditions, we further proved that

both benzaldehyde and acetophenone could be further oxidized. Understanding the feature of herein developed deep oxidation of toluene derivatives, we envisioned that different substituents at a benzylic position would not affect such oxidation. Therefore, we further investigated the oxidation reaction of benzyl derivatives with different functionalities (Fig.4d). To our delight, all tested hetero atom substituted toluene derivatives, including benzylic chloride 14, benzyloxy methane 15, benzyl(methyl)sulfane 16, benzyl-trimethyl silane 17, and benzylic borolane 18 was oxidized in this system as expected, and all gave benzoic acid 2a as the same sole product. These results detailed that both the C-H oxidation and the C-X bond cleavage taken place under standard conditions.

Article In conclusion, we have successfully developed a

general and practical photocatalytic protocol for deep aerobic oxidation of (poly)alkylbenzene. To use the inexpensive and earth-abundant CeCl3 as the catalyst, CCl3CH2OH as HAT reagent, benzyl C-H, C-C bond, C-X bonds were cleaved and finally oxidized to benzoic acid when irradiated with LED light under O2 atmosphere. The chemistry here showed good functional group tolerance and could be used as an efficient strategy in the late-stage modification in druggable molecules. Mechanistic studies unveiled the oxidation initiated from the hydrogen abstraction at the benzylic position. Thus the presence of benzyl C-H bond was the critical requirement to proceed this chemistry. Not only does this development provides a green and efficient protocol to produce the valuable substituted benzoic acids, heteroaromatic carboxylic acids and benzene polycarboxylic acids (BPCAs), but it offers new thinking to oxidize the aliphatic C-H bonds to oxygenated products from feedbacks of petroleum chemistry.

AUTHOR INFORMATION

Corresponding Author [email protected], [email protected], [email protected]

ACKNOWLEDGMENT

We thank the National Nature Science Foundation of China. This work was supported by NSFC (21988101, 21761132027, 22071029), Science and Technology Commission of Shanghai Municipality (19XD1400800, 18JC1411300), Shanghai Municipal Education Commission (2017-01-07-00-07-E00058), Key-Area Research and Development Program of Guangdong Province (2020B010188001), Shanghai Gaofeng & Gaoyuan Project for University Academic Program Development, and the China Postdoctoral Science Foundation (2020M681144). We thank Xue-Chen Luan (Fudan University) for help editing the manuscript.

AUTHOR CONTRIBUTIONS

S.Z-J. and L.F. directed the research and developed the concept of the reaction with W.C-C., who also performed the experiments and characterized all the products. Z.G-X., Z.Z-W., Z.R., and Z.D-D. gave some helpful suggestions for the reaction and analyze the results . S.Z-J. and L.F. wrote the manuscript with contributions from the other authors. COMPETING INTERESTS

The authors declare no competing interests.

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28 Schultz, D. M. & Yoon, T. P. Solar Synthesis: Prospects in Visible Light Photocatalysis. Science 343, 1239176, doi:10.1126/science.1239176 (2014).

29 Romero, N. A. & Nicewicz, D. A. Organic Photoredox Catalysis. Chemical Reviews 116, 10075-10166, doi:10.1021/acs.chemrev.6b00057 (2016).

30 Yu, X.-Y., Chen, J.-R. & Xiao, W.-J. Visible Light-Driven Radical-Mediated C–C Bond Cleavage/Functionalization in Organic Synthesis. Chemical Reviews, doi:10.1021/acs.chemrev.0c00030 (2020).

31 Shu, C., Noble, A. & Aggarwal, V. K. Metal-free photoinduced C(sp3)–H borylation of alkanes. Nature 586, 714-719, doi:10.1038/s41586-020-2831-6 (2020).

32 Pipal, R. W. et al. Metallaphotoredox aryl and alkyl radiomethylation for PET ligand discovery. Nature, doi:10.1038/s41586-020-3015-0 (2020).

33 McAtee, R. C., Noten, E. A. & Stephenson, C. R. J. Arene dearomatization through a catalytic N-centered radical cascade reaction. Nature

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34 Chambers, R. C. & Hill, C. L. Excited states of polyoxometalates as oxidatively resistant initiators of hydrocarbon autoxidation. Selective production of hydroperoxides. Inorganic Chemistry 28, 2509-2511, doi:10.1021/ic00312a002 (1989).

35 Tripathi, S., Singh, S. N. & Yadav, L. D. S. Visible light photocatalysis with CBr4: a highly selective aerobic photooxidation of methylarenes to aldehydes. RSC Advances 6, 14547-14551, doi:10.1039/C5RA26623H (2016).

36 Schultz, D. M. et al. Oxyfunctionalization of the Remote C−H Bonds of Aliphatic Amines by Decatungstate Photocatalysis. Angewandte Chemie International Edition 56, 15274-15278, doi:https://doi.org/10.1002/anie.201707537 (2017).

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39 Tanwar, L., Börgel, J. & Ritter, T. Synthesis of Benzylic Alcohols by C–H Oxidation. Journal of the American Chemical Society 141, 17983-17988, doi:10.1021/jacs.9b09496 (2019).

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41 An, Q. et al. Cerium-Catalyzed C–H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents. Journal of the American Chemical Society 142, 6216-6226, doi:10.1021/jacs.0c00212 (2020).

42 Rivaton, A. & Gardette, J.-L. Photooxidation of aromatic polymers. Angewandte Makromolekulare Chemie - ANGEW MAKROMOL CHEM 261, 173-188, doi:10.1002/(SICI)1522-9505(19981201)261-262:13.3.CO;2-F (1998).

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S1

Supporting Information for

Visible-Light-Induced Deep Aerobic Oxidation of Alkyl

Aromatics

Chang-Cheng Wang, Guo-Xiang Zhang, Zhi-Wei Zuo, Rong Zeng, Dandan Zhai, Feng Liu and Zhang-Jie Shi

I General considerations S1

II Optimization of the reaction conditions S4

III General procedure of benzylic C-H bond oxidation S5

IV Synthesis and analytical data for the products S5

V Spectral data for compounds S27

(I) General consideration

1.1 Materials and methods. All commercial reagents and solvents were used as received unless otherwise

indicated. CeCl3 was purchased from 3A Chemicals. 2,2,2-trifluoroethanol were purchased from Adamas. CH3CN was purchased from Sinopharm Chemical Reagent Co., Ltd. Other reagents were purchased from Aldrich, TCI, Adamas and J&K chemical. 1H NMR (400 MHz), 13C NMR (100 MHz) were registered on Bruker 400 M spectrometers with CDCl3 or DMSO as solvent and tetramethylsilane (TMS) as internal standard. Data are presented as follows: chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, dd = doublet of doublets, m = multiplet, br = broad), coupling constant J (Hz) and integration. Column chromatography was performed on silica gel 200-300 meshes. HRMS were performed by the Stateauthorized Analytical Center in Fudan University.

1.2 Detailed description of the LED light source and photoreactor.

1.2.1 Detailed description of the 400 nm LED lights.

S2

The LED light with an adjustable power output controller (0-10W) was purchased from WATTCAS. Water cooling was enforced for effective thermal management to maintain luminous efficiency and life expectancy of LED lights.

The photocatalytic reaction were performed on WATTCAS photoreactor (WP-TEC-1020HSL).

Figure S1. The spectrum of the LED light.

Figure S2. The detailed picture of the photoreactor.

S3

1.2.2 Detailed description of the 390 nm LED lights.

The LED light was purchased from Shanghai Yaosai Instruments Co., Ltd. The reaction vial was then irradiated with a 40W Kessil PR160L-390 nm.

Figure S3. The detailed picture of the photoreactor.

S4

(II) Optimization of the reaction conditions

COOH

hv, solvent, time (h)

cerium catalystalcohol catalystCH3

Ph Ph

Entry Alcohol catalyst Time (h) SolventT (oC) Yield (%)b

1

2

3

4

5

6

7

8

9

EtOH 60 CH3CN12 21CeCl3

EtOH 60 CH3CN12 12Ce(OTf)3

EtOH 60 CH3CN12 < 5Ce(OH)4

EtOH 60 CH3CN12 10Ce(NH4)2(NO3)6

CCl3CH2OH 60 CH3CN12 54CeCl3

HFIP 60 CH3CN12 25CeCl3

CCl3CH2OH RT CH3CN12 22CeCl3

CCl3CH2OH 100 CH3CN12 < 5CeCl3

CCl3CH2OH 60 DMSO24 < 5CeCl310

CCl3CH2OH 60 H2O24 N.D.CeCl311

CCl3CH2OH 60 CH3CN24 92(88c)CeCl3

CCl3CH2OH 60 CH3CN24 N.D.-

12

light

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

400 nm

CCl3CH2OH 60 CH3CN24 N.D.CeCl313 dark

3n 4n

[Ce]

a Reaction condition: 1a (0.1 mmol), cerium catalyst (5.0 mol%), alcohol catalyst (20.0 mol%), and solvent (2.0 mL). b The yield was determined based on 1H NMR with CH2Br2 as a standard internal compound. c Isolated yield.

S5

(III) General procedure

CH3 COOH

CH3CN, 1 atm O2, 60

oC

400 nm LED (10 W)

CeCl3 (5 mol%)

CCl3CH2OH (20 mol%)

1a 2a

A 25mL quartaz glass tube was charged with a stiring bar, and added reagent 1a (0.1 mmol, 0.0092 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.

(IV) Synthesis and analytical data for the products Compound (2a) : benzoic acid.

Procedure : The title compound was synthesized via General Procedure for 24 hours.

10.3 mg, 84%. 1H NMR (400 MHz, DMSO) δ 12.95 (s, 1H), 7.99-7.91 (m, 2H), 7.65-7.59 (m, 1H), 7.50 (t, J = 7.6 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 167.7, 133.2, 131.1, 129.6, 128.9.

The spectroscopic data match a literature report (Green Chem. 2018, 20, 3038).

Compound (2b) : isobenzofuran-1,3-dione.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1b (0.1 mmol, 0.0106 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (1.0 equiv. 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 1:1) to give the corresponding product.

9.6 mg, 65%. 1H NMR (400 MHz, DMSO) δ 8.02-8.04 (m, 2H), 7.91-7.93 (m, 2H).). 13C NMR (100 MHz, DMSO) δ 162.8, 136.0, 131.3, 125.7.

The spectroscopic data match a literature report (Org. Lett. 2014, 16, 1108).

COOH

O

O

O

S6

Compound (2c) : isophthalic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1c (0.1 mmol, 0.0106 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

14.1 mg, 85%. 1H NMR (400 MHz, DMSO) δ 13.26 (s, 2H), 8.48 (s, 1H), 8.17 (s, 2H), 7.65 (s, 1H). 13C NMR (100 MHz, DMSO) δ 167.1, 133.9, 131.7, 130.4, 129.7.


Compound (2d) : terephthalic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1d (0.1 mmol, 0.0106 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 48 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with ethyl acetate to give the corresponding product.

14.2 mg, 86%. 1H NMR (400 MHz, DMSO) δ 13.23 (s, 2H), 8.03 (s, 4H). 13C NMR (100 MHz, DMSO) δ 167.2, 135.0, 129.9.


Compound (2e) : benzene-1,2,3-tricarboxylic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1e (0.1 mmol, 0.0120 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

COOH

COOH

COOH

COOH

S7

12.4 mg, 59%. 1H NMR (400 MHz, DMSO) δ 12.69 (s, 1H), 8.02 (d, J = 7.6 Hz, 2H), 7.60 (t, J = 7.6 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 169.1, 167.3, 137.2, 133.4, 130.4, 129.4.


Compound (2f) : benzene-1,2,4-tricarboxylic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1f (0.1 mmol, 0.0120 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with ethyl acetate and the corresponding product was dissolved in ethyl acetate.

12.5 mg, 60%. 1H NMR (400 MHz, D2O) δ 8.38 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 168.8, 168.0, 166.5, 138.0, 132.9, 132.5, 132.2, 130.2, 129.5.

The spectroscopic data match a literature report (Angew. Chem. Int. Ed. 2020, 59, 1263).

Compound (2g) : benzene-1,3,5-tricarboxylic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1g (0.1 mmol, 0.0120 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 72 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.


The spectroscopic data match a literature report (Chem. Commun. 2018, 54, 11574).

COOH

COOHHOOC

COOH

COOHCOOH

COOH

HOOC COOH

S8

Compound (2h) : benzene-1,2,3,4-tetracarboxylic acid

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1h (0.1 mmol, 0.0134 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

23.4 mg, 75%. 1H NMR (400 MHz, DMSO) δ 13.24 (s, 4H), 7.90 (s, 2H). 13C NMR (100 MHz, DMSO) δ 168.3, 167.3, 134.4, 133.7, 130.4.

The spectroscopic data match a literature report (JFE Chemical Corporation - EP2135856, 2009).

Compound (2i) : benzene-1,2,4,5-tetracarboxylic acid

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1i (0.1 mmol, 0.0134 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

20.1 mg, 79%. 1H NMR (400 MHz, D2O) δ 12.11 (s, 4H), 7.97 (s, 2H). 13C NMR (100 MHz, D2O) δ 172.9, 135.9, 128.6.

The spectroscopic data match a literature report (Green Chem., 2017, 19, 1663).

Compound (2j) : benzene-1,2,3,5-tetracarboxylic acid

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1j (0.1 mmol, 0.0134 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 390 nm LED lights (40W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

COOH

COOH

HOOC

HOOC

COOH

COOHHOOCCOOH

S9

16.5 mg, 65%. 1H NMR (400 MHz, D2O) δ 8.69 (s, 2H).

13C NMR (100 MHz, D2O) δ 173.0, 167.7, 167.4, 140.3, 135.4, 131.4, 128.9.

The spectroscopic data match a literature report (10.1002/hlca.200690260).

Compound (2k) : benzene-1,2,3,4,5-pentacarboxylic acid

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1k (0.1 mmol, 0.0148 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 390 nm LED lights (40W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

20.6 mg, 69%. 1H NMR (400 MHz, D2O) δ 12.59 (s, 5H), 8.59 (s, 1H). 13C NMR (100 MHz, D2O) δ 171.6, 167.4, 138.6, 134.1, 130.0.

The spectroscopic data match a literature report (Chem. Eu. J. 2020, 26, 11250).

Compound (2l) : hexamethyl benzene-1,2,3,4,5,6-hexacarboxylate.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1l (0.1 mmol, 0.0162 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 390 nm LED lights (40W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, added CH3I and stirred overnight at room temperature. Then, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 10:1) to give the corresponding product.

20.8 mg, 49%. 1H NMR (400 MHz, CDCl3) δ 3.88 (s, 18H). 13C NMR (100 MHz, CDCl3) δ 165.1, 133.9, 53.5.

The spectroscopic data match a literature report (MedChemComm. 2019, 10, 1476).

COOH

COOH

HOOC

HOOCCOOH

COOMe

COOMe

MeOOC

MeOOC

COOMe

COOMe

COOH

COOHHOOC

COOH

S10

Compound (4a) : 2-methoxybenzoic acid.


9.9 mg, 65%. 1H NMR (400 MHz, DMSO) δ 12.58 (s, 1H), 7.62 (dd, J = 7.6, 1.8 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 3.81 (s, 3H). 13C NMR (100 MHz, DMSO) δ 167.7, 158.4, 133.4, 131.0, 121.6, 120.3, 112.7, 56.0.


Compound (4b) : 4-methoxybenzoic acid.


11.9 mg, 78%. 1H NMR (400 MHz, DMSO) δ 12.61 (s, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H). 13C NMR (100 MHz, DMSO) δ 167.1, 162.9, 131.4, 123.0, 113.9, 55.5.


Compound (4c) : 4-acetoxybenzoic acid.


14.5 mg, 80%. 1H NMR (400 MHz, DMSO) δ 13.05 (s, 1H), 7.99 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 2.29 (s, 3H). 13C NMR (100 MHz, DMSO) δ 169.0, 166.8, 154.1, 131.0, 128.4, 122.2, 21.0.


Compound (4d) : 4-(isobutyryloxy)benzoic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 3d (0.1 mmol, 0.0178 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently,

COOHMeO

COOH

OMe

COOH

OAc

S11

the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 1:1) to give the corresponding product.

14.9 mg, 72%. 1H NMR (400 MHz, DMSO) δ 13.07 (s, 1H), 7.99 (d, J = 7.2 Hz, 2H), 7.25 (d, J = 7.2 Hz, 2H), 2.84 (m, 1H), 1.24 (dd, J = 7.2, 1.2 Hz, 6H). 13C NMR (100 MHz, DMSO) δ 174.8, 166.7, 154.2, 131.0, 128.4, 122.1, 33.5, 18.7.

The spectroscopic data match a literature report (Green Chem., 2018, 20, 3038).

Compound (4e) : 4-(benzoyloxy)benzoic acid.

The title compound was synthesized via General Procedure for 24 hours.

16.5 mg, 68%. 1H NMR (400 MHz, DMSO) δ 13.09 (s, 1H), 8.15 (d, J = 7.2 Hz, 2H), 8.05 (d, J = 8.8 Hz, 2H), 7.76 (t, J = 7.6 Hz, 1H), 7.62 (t, J = 7.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 166.2, 163.8, 153.6, 133.8, 130.5, 129.4, 128.6, 128.1, 128.1, 121.8.

The spectroscopic data match a literature report (J. Phys. Org. Chem. 2016, 30, 3608).

Compound (4f) : 4-(tert-butyl)benzoic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 3f (0.1 mmol, 0.0148 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 1:1) to give the corresponding product.

7.2 mg, 40%. 1H NMR (400 MHz, DMSO) δ 12.44 (s, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 1.28 (s, 9H). 13C NMR (100 MHz, DMSO) δ 167.6, 156.1, 129.5, 128.4, 125.7, 35.1, 31.2.


COOH

OO

COOH

OBz

t-Bu

COOH

S12

Compound (4g) : 4-(trifluoromethyl)benzoic acid.


17.1 mg, 90%. 1H NMR (400 MHz, DMSO) δ 13.41 (s, 1H), 8.13 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 166.3, 134.7, 133.1 (q, J = 31.0 Hz), 130.2, 128.0, 125.7, 125.3, 122.6. 19F NMR (376 MHz, DMSO) δ -61.7.


Compound (4h) : 4-nitrobenzoic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 3h (0.1 mmol, 0.0137 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 48 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 1:1) to give the corresponding product.

3.8 mg, 21%. 1H NMR (400 MHz, DMSO) δ 13.62 (s, 1H), 8.33 (d, J = 8.8 Hz, 2H), 8.17 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 166.2, 150.4, 136.7, 131.0, 124.1.


Compound (4i) : 4-fluorobenzoic acid.


14.9 mg, 81%. 1H NMR (400 MHz, DMSO) δ 13.03 (s, 1H), 8.04-7.96 (m, 2H), 7.35-7.27 (m, 2H). 13C NMR (100 MHz, DMSO) δ 166.5 (d, J = 220 Hz), 163.8, 132.3 (d, J = 9.0 Hz), 127.5, 115.8 (d, J = 22.0 Hz). 19F NMR (376 MHz, DMSO) δ -106.9.

COOH

CF3

COOH

NO2

COOH

F

S13


Compound (4j) : 4-chlorobenzoic acid.




Compound (4k) : 4-bromobenzoic acid.




Compound (4l) : 4-(ethoxycarbonyl)benzoic acid.


14.0 mg, 72%. 1H NMR (400 MHz, DMSO) δ 13.20 (s, 1H), 8.04 (s, 4H), 4.33 (q, J = 7.2 Hz, 2H), 1.32 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, DMSO) δ 166.7, 165.2, 134.9, 133.5, 129.7, 129.4, 61.3, 14.2.

The spectroscopic data match a literature report (J. Am. Chem. Soc. 2013, 135, 2891).

Compound (4m) : 4-cyanobenzoic acid.


COOH

Cl

COOH

Br

COOH

CO2Et

S14

10.6 mg, 78%. 1H NMR (400 MHz, DMSO) δ 13.53 (s, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 166.1, 135.0, 132.8, 130.0, 118.3, 115.2.


Compound (4n) : [1,1'-biphenyl]-4-carboxylic acid.


17.5 mg, 88%. 1H NMR (400 MHz, DMSO) δ 13.04 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 167.3, 144.4, 139.2, 130.1, 129.7, 129.2, 128.4, 127.1, 126.9.


Compound (4o) : [1,1'-biphenyl]-3-carboxylic acid.


19.5 mg, 92%. 1H NMR (400 MHz, DMSO) δ 13.05 (s, 1H), 8.17 (s, 1H), 7.95-7.88 (m, 2H), 7.68 (d, J = 7.6 Hz, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.39 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 167.4, 140.6, 139.4, 131.6, 131.2, 129.5, 129.2, 128.7, 128.4, 128.0, 127.4, 126.9.

The spectroscopic data match a literature report (Adv. Synth. Catal. 2010, 352, 1075).

Compound (4p) : 3-fluorobenzoic acid.


11.6 mg, 83%. 1H NMR (400 MHz, DMSO) δ 13.21 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.68-7.63 (m, 1H), 7.58-7.53 (m, 1H), 7.48-7.45 (m, 1H). 13C NMR (100 MHz, DMSO) δ 166.6 (d, J = 2.8 Hz), 161.2 (d, J = 243.2 Hz), 133.6 (d, J

COOH

CN

COOH

Ph

COOH

F

COOH

Ph

S15

= 7.2 Hz), 131.3 (d, J = 7.9 Hz), 125.8 (d, J = 2.8 Hz), 120.2 (d, J = 21.0 Hz), 116.0 (d, J = 22.5 Hz). 19F NMR (376 MHz, DMSO) δ -112.58, -112.60, -112.61.


Compound (4q) : 3-chlorobenzoic acid.


10.9 mg, 70%. 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 170.9, 134.7, 133.9, 131.0, 130.3, 129.9, 128.3.

The spectroscopic data match a literature report (J. Org. Chem. 2014, 79, 6094).

Compound (4r) : 2-fluorobenzoic acid.


8.5 mg, 61%. 1H NMR (400 MHz, CDCl3) δ 8.04 (t, J = 7.6 Hz, 1H), 7.59 (dd, J = 13.6, 7.2 Hz, 1H), 7.25-7.15 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 169.9 (d, J = 3 Hz), 163.9 (d, J = 261 Hz), 135.6 (d, J = 10 Hz), 132.75, 124.1 (d, J = 3 Hz), 117.5 (d, J = 9 Hz), 117.2 (d, J = 22 Hz). 19F NMR (376 MHz, DMSO) δ -108.3 - -108.4.

The spectroscopic data match a literature report (Chem. Eur. J. 2016, 22, 3758).

Compound (4s) : 4-bromo-2-(trifluoromethyl)benzoic acid.


24.1 mg, 87%. 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 6.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 170.5, 135.0, 132.9, 131.9, 130.5, 130.4, 127.1.

The spectroscopic data match a literature report (Bioorg. Med Chem. 2007, 15, 2198).

Compound (4t) : 4-chloro-3-fluorobenzoic acid.

COOHCF3

Br

COOH

Cl

COOHF

S16


14.7 mg, 84%. 1H NMR (400 MHz, DMSO) δ 13.43 (s, 1H), 7.83 (d, J = 10.8 Hz, 1H), 7.80-7.71 (m, 2H). 13C NMR (100 MHz, DMSO) δ 166.0 (d, J = 8.0 Hz), 156.27 (d, J = 52.0 Hz), 132.42 (d, J = 28 Hz), 131.56, 126.95 (d, J = 16.0 Hz), 125.02 (d, J = 68.0 Hz), 117.86 (d, J = 88.0 Hz). 19F NMR (376 MHz, DMSO) δ -115.14, -115.16, -115.16, -115.18.

The spectroscopic data match a literature report (Bioorg. Med Chem. 2007, 15, 2198).

Compound (4u) : 2,3-dichlorobenzoic acid.


15.8 mg, 82%. 1H NMR (400 MHz, DMSO) δ 13.13 (s, 1H), 7.80 (dd, J = 8.0, 1.2 Hz, 1H), 7.70 (dd, J = 7.6, 1.2 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 166.9, 135.0, 133.3, 133.2, 131.6, 129.3, 129.0.

The spectroscopic data match a literature report (Magn. Reson. Chem. 2007, 45, 1035).

Compound (4v) : 3,5-dichlorobenzoic acid.


14.9 mg, 78%. 1H NMR (400 MHz, DMSO) δ 12.82 (s, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 7.85 (s, 1H). 13C NMR (100 MHz, DMSO) δ 165.4, 135.0, 134.8, 132.7, 128.3.

The spectroscopic data match a literature report (10.1007/s10870-020-00822-9).

Compound (4w) : 3-bromo-5-(methoxycarbonyl)benzoic acid.


White solid. (21.8 mg, 84%); 1H NMR (400 MHz, DMSO) δ 8.39 (t, J = 1.2 Hz, 1H), 8.25 (m, 2H), 3.89 (s, 3H). 13C COOH

Br O

O

COOH

ClF

COOHCl

Cl

COOH

ClCl

S17

NMR (100 MHz, DMSO) δ 165.6, 164.6, 136.5, 135.9, 134.0, 132.6, 129.0, 122.6, 53.3.

The spectroscopic data match a literature report (J. Am. Chem. Soc. 2003, 125, 10241).

Compound (4x) : 2,3,5,6-tetrafluorobenzoic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 3x (0.1 mmol, 0.0164 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 48 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether/ethyl acetate = 1:1) to give the corresponding product.

5.1 mg, 27%. 1H NMR (400 MHz, D2O) δ 7.29 (tt, J = 10.4, 7.6 Hz, 1H). 13C NMR (100 MHz, D2O) δ 166.34, 147.02 (m, J = 16 Hz), 144.57 (m, J = 16 Hz), 143.43 (m, J = 16 Hz), 141.00 (m, J = 16 Hz), 105.92 (t, J = 92 Hz). 19F NMR (377 MHz, D2O) δ -139.04 ~ -139.26 (m), -144.85 ~ -145.15 (m).

The spectroscopic data match a literature report (Organic Electronics. 2017, 44, 85).

Compound (6a) : thiophene-2-carboxylic acid.

Procedure : The title compound was synthesized via General Procedure at 25 oC for 24 hours.

5.6 mg, 44%. 1H NMR (400 MHz, DMSO) δ 13.06 (s, 1H), 7.89 (d, J = 5.2 Hz, 1H), 7.73 (d, J = 3.6 Hz, 1H), 7.20-7.17 (m, 1H). 13C NMR (100 MHz, DMSO) δ 163.4, 135.1, 133.8, 133.7, 128.7.


Compound (6b) : 5-acetylthiophene-2-carboxylic acid.

COOH

FF

F F

SCOOH

S18

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 5b (0.1 mmol, 0.0140 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 30 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

13.9 mg, 81%. 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 3.6, 1.2 Hz, 1H), 7.62 (dd, J = 5.2, 1.2 Hz, 1H), 7.13 (dd, J = 4.6, 3.6 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 192.0, 163.0, 161.4, 148.7, 134.2, 134.1, 27.3.

The spectroscopic data match a literature report (Chem. 2020, 6, 2658).

Compound (6c) : benzo[b]thiophene-2-carboxylic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 5c (0.1 mmol, 0.0148 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 30 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

13.1 mg, 74%. 1H NMR (400 MHz, D2O) δ 8.31 (dd, J = 5.6, 2.8 Hz, 1H), 8.10-8.00 (m, 4H). 13C NMR (100 MHz, D2O) δ 172.8, 139.6, 132.4, 132.3, 131.8, 131.0, 128.7, 127.9.


Compound (6d) : 4-(pyridin-2-yl)benzoic acid.


14.1 mg, 71%. 1H NMR (400 MHz, DMSO) δ 12.96 (s, 1H), 8.80 (d, J = 5.2 Hz, 1H), 8.21 (m, 4H), 8.09 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 9.2, 4.4 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 167.3, 153.6, 147.6, 141.4, 140.1, 132.4, 130.3, 127.9, 124.9, 123.3.

The spectroscopic data match a literature report (J. Org.

SCOOH

O

COOH

N

SCOOH

S19

Chem. 2018, 83, 15486).

Compound (6e) : isonicotinic acid.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 5e (0.1 mmol, 0.0093 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 60 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by washing with acetonitrile to give the corresponding product.

6.6 mg, 54%. 1H NMR (400 MHz, DMSO) δ 13.39 (s, 1H), 8.78 (d, J = 5.2 Hz, 2H), 7.81 (d, J = 6.0 Hz, 2H). 13C NMR (100 MHz, DMSO) δ 166.7, 151.1, 138.5, 123.2.


Compound (6f) : thiophene-2-carboxylic acid.


23% (NMR yield). 1H NMR (400 MHz, CDCl3) δ 12.80 (s, 1H), 8.03 (d, J = 1.2 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.2 Hz, 2H), 7.41 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 1.2 Hz, 1H).


Synthesis of compound 2a from 7a.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 7a (0.1 mmol, 0.0106 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.

NNHOOC

N

COOH

S20



Synthesis of compound 4n from 7b.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 7b (0.1 mmol, 0.0210 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.

15.0 mg, 76%. 1H NMR (400 MHz, DMSO) δ 13.04 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 167.3, 144.4, 139.2, 130.1, 129.7, 129.2, 128.4, 127.1, 126.9.


Synthesis of compound 2a from 9a.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 9a (0.1 mmol, 0.0120 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.


O

OH

O

OH

Ph

O

OH

S21


Synthesis of compound 4k from 9b.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 9b (0.1 mmol, 0.0199 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.



Synthesis of compound 2d from 9c.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 9c (0.1 mmol, 0.0164 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.



Synthesis of compound 2d from 9d.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 9c (0.1 mmol, 0.0162 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED

COOH

Br

COOH

COOH

S22

lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.



Synthesis of compound 2a from 1a, 7a and 9a (1:1:1 mixture).

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 1a (0.1 mmol, 0.0092 g), 7a (0.1 mmol, 0.0106 g), 9a (0.1 mmol, 0.0120 g), CeCl3 (5 mol%, 0.0036 g), CCl3CH2OH 1.0 equiv, 0.0447 g), CH3CN (2 mL) under O2 atmosphere. The mixture was irradiated with a 390 nm LED lights (40W) for 24 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.



Compound (10) : Celebrex derivative.

Procedure : The title compound was synthesized via General Procedure for 24 hours and the residue was purified directly by flash column chromatography (ethyl acetate) to give the corresponding product.

26.2 mg, 65%. 1H NMR (400 MHz, DMSO) δ 12.11 (s, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.52 (s, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.35 (s, 1H). 13C NMR (100 MHz, DMSO) δ 167.0, 144.6, 144.5, 141.2,

SO

NH2O

NNF3C

COOH

COOH

COOH

O

OH

S23

132.6, 131.7, 130.0, 129.5, 127.3, 126.4, 107.4. 19F NMR (377 MHz, DMSO) δ -60.87.

The spectroscopic data match a literature report (10.1016/j.bioorg.2019.103110).

Compound (11) : 1-([1,1'-biphenyl]-4-ylmethoxy)-2,2,6,6-tetramethylpiperidine.

Procedure : A 25mL quartaz glass tube was charged with a stiring bar, and added 3n (0.1 mmol, 0.0168 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH 1.0 equiv, 0.0149 g), CH3CN (2 mL) under N2 atmosphere. The mixture was irradiated with a 400 nm LED lights (10W) for 24 hours at 60 oC. After taking out the reaction tube and freezing with liquid nitrogen. Then 3 equivalent TEMPO was added to the system. The mixture was irradiated with a 400 nm LED lights (10W) for 12 hours at 60 oC under N2 atmosphere. After completion of reaction as indicated by TLC. Subsequently, the solvent was concentrated under reduced pressure, and the residue was purified directly by flash column chromatography (petroleum ether) to give the corresponding product.

1H NMR (400 MHz, C6D6) δ 7.47-7.43 (m, 4H), 7.37 (d, J = 8.4 Hz, 2H), 7.20 (t, J = 7.6 Hz, 2H), 7.11 (d, J = 2.0 Hz, 1H), 4.92 (s, 2H), 1.47 (dd, J = 12.4, 4.8 Hz, 3H), 1.31 (s, 9H), 1.19 (s, 6H). 13C NMR (100 MHz, C6D6) δ 128.6, 127.8, 127.6, 127.3, 127.0, 126.9, 78.7, 59.7, 39.6, 33.0, 19.9, 17.0.

Compound (4n’): [1,1'-biphenyl]-4-carboxylic acid

Procedure:A 25mL quartaz glass tube was charged with a stiring bar, and added 3n (0.1 mmol, 0.0168 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (20 mol%, 20 μL (1M CH3CN solution)), CH3CN (2 mL) under 18O2 atmosphere. The mixture was place perpendicular to a 400 nm LED lights (10W) and stirred under blue light irradiation for 48 hours at 60 oC. After completion of reaction as indicated by TLC. Subsequently, ethyl acetate and water were added to extract for three times. The organic phase was concentrated under reduced pressure to give the corresponding product.

16.6 mg, 82%. 1H NMR (400 MHz, DMSO) δ 13.04 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO) δ 167.3, 144.4, 139.2, 130.1, 129.7, 129.2, 128.4, 127.1, 126.9. HRMS ESI (m/z) calcd for C13H10

18O2 [M-H] 201.0687, Found: 201.0696.

ON

Ph

Ph

18OH

18O

S24


Kinetic experiments.

Ph

CeCl3 (5.0 mol%)

CCl3CH2OH (1.0 equiv.)

CD3CN, O2 (balloon)

390 nm LED (40 W)Ph Ph

CHO

Ph

COOH+O +

OH

3n 12 13 4n

A 25mL quartaz glass tube was charged with a stiring bar, and added 3p (0.1 mmol, 0.0168 g), CeCl3 (5 mol%, 0.0012 g), CCl3CH2OH (1.0 equiv. 0.0149 g), CD3CN (2 mL) under 18O2 atmosphere. The mixture was place perpendicular to a 390 nm LED lights (40W) and stirred under blue light irradiation at 60 oC and measured the NMRs every 15 minutes.

Benzaldehyde oxidation reaction

H

O

CH3CN, O2, 60 oC12 h

OH

O

1

2

3

4

5

CeCl3 CCl3CH2OH 400 nm

5%

5%

5%

20%

yield (%)b

20%

20%

92

N.R.

bThe yield was determined based on 1H NMR with CH2Br2

as a standard internal compound.

86

88

95

entry

Acetophenone oxidation reaction

S25

O

CH3CN, O2, 60 oC24 h

OH

O

1

2

3

4

5

CeCl3 CCl3CH2OH hv

5%

5%

5%

20%

yield (%)b

20%

20%

entry

N.R.

N.R.

85

N.R.

N.R.

bThe yield was determined based on 1H NMR with CH2Br2

as a standard internal compound.

Synthesis of compound 2a from 14








COOH

COOH

S26













COOH

COOH

COOH

S27

(V) Spectral data for compounds Compound (2a) : benzoic acid.

S28

Compound (2b) : isobenzofuran-1,3-dione.

S29

Compound (2c) : isophthalic acid.

S30

Compound (2d) : terephthalic acid.

S31

Compound (2e) : benzene-1,2,3-tricarboxylic acid.

S32

Compound (2f) : benzene-1,2,4-tricarboxylic acid.

S33

Compound (2g) : benzene-1,3,5-tricarboxylic acid.

S34

Compound (2h) : benzene-1,2,3,4-tetracarboxylic acid

S35

Compound (2i) : benzene-1,2,4,5-tetracarboxylic acid

S36

Compound (2j) : benzene-1,2,3,5-tetracarboxylic acid

S37

Compound (2k) : benzene-1,2,3,4,5-pentacarboxylic acid

S38

Compound (2l) : benzene-1,2,3,4,5,6-hexacarboxylic acid

S39

Compound (4a) : 2-methoxybenzoic acid.

S40

Compound (4b) : 4-methoxybenzoic acid.

S41

Compound (4c) : 4-acetoxybenzoic acid.

S42

Compound (4d) : 4-(isobutyryloxy)benzoic acid.

S43

Compound (4e) : 4-(benzoyloxy)benzoic acid.

S44

Compound (4f) : 4-(tert-butyl)benzoic acid.

S45

Compound (4g) : 4-(trifluoromethyl)benzoic acid.

S46

Compound (4h) : 4-nitrobenzoic acid.

S47

Compound (4i) : 4-fluorobenzoic acid.

S48

Compound (4j) : 4-chlorobenzoic acid.

S49

Compound (4k) : 4-bromobenzoic acid.

S50

Compound (4l) : 4-(ethoxycarbonyl)benzoic acid.

S51

Compound (4m) : 4-cyanobenzoic acid.

S52

Compound (4n) : [1,1'-biphenyl]-4-carboxylic acid.

S53

Compound (4o) : [1,1'-biphenyl]-3-carboxylic acid.

S54

Compound (4p) : 3-fluorobenzoic acid.

S55

Compound (4q) : 3-chlorobenzoic acid.

S56

Compound (4r) : 2-fluorobenzoic acid.

S57

Compound (4s) : 4-bromo-2-(trifluoromethyl)benzoic acid.

S58

Compound (4t) : 4-chloro-3-fluorobenzoic acid.

S59

Compound (4u) : 2,3-dichlorobenzoic acid.

S60

Compound (4v) : 3,5-dichlorobenzoic acid.

S61

Compound (4w) : 3-bromo-5-(methoxycarbonyl)benzoic acid.

S62

Compound (4x) : 2,3,5,6-tetrafluorobenzoic acid.

S63

Compound (6a) :thiophene-2-carboxylic acid.

S64

Compound (6b) : 5-acetylthiophene-2-carboxylic acid.

S65

Compound (6c) : benzo[b]thiophene-2-carboxylic acid.

S66

Compound (6d) : 4-(pyridin-2-yl)benzoic acid.

S67

Compound (6e) : isonicotinic acid.

S68

Compound (10) : Celebrex derivative.

S69

Compound (11) : 1-([1,1'-biphenyl]-4-ylmethoxy)-2,2,6,6-tetramethylpiperidine.

S70

Figure 4b Kinetic experiments

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visible-light-induced deep aerobic oxidation ... - amazon s3

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