Altering Substituents of Pyrylium Salt PhotocatalystsA Bright Future for Photoredox Chemistry

Photoredox chemistry is an incredibly powerful branch of chemistry that depends on

powering chemical reactions utilizing readily-available light - and is made possible with recent

technological advances in LED lighting and specific wavelengths that can be used to activate

molecules of interest in reactions.2 In current photoredox chemistry, iridium and ruthenium are

reported as heavily-used catalysts with long redox windows, but due to the unsustainability of

these inorganic catalysts, it is integral to develop and explore the utility of alternate, organic

catalysts.3 Three sets of physically stable, powerful pyrylium salt catalysts with differing

substituents were generated and tested with blue light to quantify photocatalytic properties,

including reduction potentials and absorption/fluorescence spectra.1 Further generation and

analysis of subsequent photoredox compounds are integral for chemists to make more effective,

lower-cost catalysts, choosing optimal ones based on reduction properties to develop thousands

of potential compounds that can be used in meaningful ways, such as in medical applications to

be screened against diseases.

    Many reactions, due to high activation energies, proceed slowly and may require input of

extra energy to be kinetically viable. Facilitating reactions such as these is one of the many

applications of catalysts. Using these, reactions can take place at cooler temperatures than

usual, saving energy, and in several cases increasing yield substantially.2 Additionally, because

it is regenerated in the reaction, a single catalyst can produce a large number of many useful

chemicals. One such category of catalyst is particularly useful in redox reactions. Photoredox

catalysts use abundant light energy to fuel the reactions they facilitate. The catalyst becomes a

potent oxidizing agent when photons excite its electrons to higher energy states, causing it to

react with its substrate and generate highly-reactive reagent intermediates.1 Sourcing the energy

in this way saves power that would otherwise be used to heat solutions which can additionally

cause undesired side reactions.4

Photoredox chemistry has grown tremendously in the past decade thanks to the

discovery and synthesis of organic photocatalysts such as acridinium-based salts. These

molecules have many of the same advantages as the transition metal-based photocatalysts

they replace, namely wider redox windows and increased physical stability, while also being

more soluble in organic solvents and resistant to pH changes and bleaching effects.3 They have

been utilized in previous studies exploring the synthesis of lepidine with noted success, and

carry chemical applications in medicines such as Tylenol, photovoltaic devices, and solar-

powered technology.7

Pyrylium salts are another category of organic photocatalysts with similar properties to

acridinium. They are advantageous over polypyridyl complexes based on rare and expensive

elements Ruthenium and Iridium in that they are both cost-effective and sustainable, and thus

much easier to mass-produce.3 One of the only obstacles remaining for the widespread use of

this easily-produced, sustainable group of catalysts is uncertainty regarding the properties.

Different substituent groups on the pyrylium’s three aryl groups can affect its electrochemical

properties in both excited and ground states. The purpose of this experiment is to investigate

the effects of several substituent groups and generate trends, which, in addition to identifying

the effects of the specific groups tested, can be useful in the future prediction and synthesis of

an optimal pyrylium photocatalyst.

Figure 1: Pyrylium salt with potential R substituents for manipulation in experimentation to test subsequent photochemical properties. In subsequent experimentation, R1 is changed three separate times (fluorine, methoxy, and methyl as function groups), while R2 and R3 are

showcased as methyl groups. The orientation of substituents upon these three sets of pyrylium salts allows for a viable comparison to be made.

Figure 2: UV-Vis absorbance and emission spectra for A1 Pyrylium.

Table 1: Average data points compounded from students of twenty-six lab sections in Chemistry 262L for three salt forms for UV-Vis, fluorescence, and CV.

Pyrylium: A1 A2 A3

Absorbance λmax 427.2 nm 418.5 nm 422.0 nm

Emission λmax 489 nm 485.3 nm 484.9 nm

E1/2 -263.7 mV -279.4 mV -333.5 mV

Figure 3: A cyclic voltammogram for A1 pyrylium. A second redox peak is shown, but not analyzed for photochemical properties.

Table 2: Table of calculated values. The E*1/2 values were generated comparatively to the SCE.

Pyrylium A1 A2 A3

E0,0 2.685V 2.722V 2.713V

E*1/2 2.421V 2.443V 2.379V

    Table 3: Oxidation yields of acetophenone following reaction of 1-phenylethanol with catalytic salts

Pyrylium A1 A2 A3

Oxidation Yield 34.9% 48.2% 31.2%

The above results show little quantitative distinction between catalytic capabilities of

pyrylium salts A1, A2, and A3. The range of values for all three salts, 2.38V to 2.42V, is

comparable to good reducing catalysts as previously determined by studies of acridinium salts.3

These values corroborate their utility compared to previous catalysts studied (1.0V – 2.0V

range).3 Successful alcohol oxidation was showcased through NMR data and comparison to

controls: a) no catalyst present underneath blue light (no acetophenone formed), and catalyst

present under no blue light (no acetophenone formed).

Salts A1 and A2’s reduction potential values differ by 0.022V (22 mV), A2 and A3 by

0.064V (64 mV), and A1 and A3 by 0.042V (42 mV). The greatest distinction is found between

A2 and A3; having three methyl groups present as R substituents versus having two methyls

and one methoxy group. Additionally, A2 produced the highest yield of product in the test

reaction (48.1%), greater than the A1’s yield by 13.3%, and A3 yield’s by 17.0%. By these

associations, A2 is comparatively the strongest oxidizing pyrylium salt. The highest reduction

potential value quantifies the highest oxidizing compound. A2 is distinguished comparatively as

less electron-donating in nature compared to salts A1 and A3.

Salt A1 contains the substituent of fluorine, which engages in dual electrochemical

manners. Fluorine is intensely electronegativity, but can also partake in electron-donation. It is a

halogen and acts in an ortho-para structure, which could explain its dichotomous electronic

properties.7 In previous experiments, fluorine is shown to modify the HOMO and LUMO states of

base derivatives, which could alter calculations.8 It generates the second-highest yield of

acetophenone, at a value of 34.9%, indicative of oxidative qualities. Due to its withdrawing and

donating characteristics, the electrochemical nature of this catalyst is more unstable compared

to that of salt A2.

A3 contains the electron-donating methoxy substituent, which could explain this

compound’s less optimal reductive ability compared to salt A2: lone pairs are available for

donation from an electronic perspective, which occupies more orbital space, reducing the

oxidative capacity for this salt to take on another electron. In comparison, A2’s neutral methyl

substituent does not classify as particularly electron-withdrawing or donating, explaining the

highest oxidative yield and highest reduction potential relative to the other two salts of interest.It is possible that catalytic degradation took place in some of these reactions, leading to

an error in reported values. In a second run-through of experiments, the A1 reaction mixture was cloudy in appearance, and not the desired neon yellow color. Additionally, improprieties in procedure were noted, such as the generation of a large amount of more impure (lighter-orange, sandy) A1 pyrylium salt catalyst. Only the minority, more pure (dark orange, paste-like) catalyst was used. Very precise dilutions were necessary for accurate cyclic voltammetry values to be

taken, and could have been another source of error.1

    These observations underscore how effective additional alterations influence the catalytic

behavior of photoredox compounds similar to these three preliminary pyrylium salts studied,

with A2 resulting as the strongest oxidizer. A promising reduction potential range of 2.38 to

2.42V (strong cayatics) was showcased in the three salts powered via visible light. The

variations in reduction potential values and oxidation yields and subsequent examination of

electronic causes of these shifts confirm the significance of studying changed substituents.

Though characteristics of only three pyrylium salts were collected, this information can be used

to generate subsequent trends and hypotheses regarding untested substituents.

Future research can include more photochemical analyses of properties. Characteristics

such as effective reads of substrate decomposition will be integral to maintaining accuracy in

the database of catalysts created. The testing and confirmation of identified patterns will be

used to generate optimal photocatalysts for the many device, medicinal, and chemical situations

that are pertinent in photoredox chemistry. Though the salts tested above absorbed blue

wavelengths of light (455nm LED), orange and yellow light are also cited to be high-energy in

photoredox reactions and can be used to generate further reduction potentials.4 Flow reactor

studies for future pyrylium salts could be also be quantified. This is useful when thinking about

the scale of massive compound generation.2

In conclusion, a series of substituted salts were generated and provide promising

evidence for future photochemical analyses with additional photoredox catalytic salts.

Generating trends of data focused on absorbance, emission, and reduction values, as well as

other additional identified variables, can be useful in the future prediction and synthesis of an

optimal pyrylium photocatalyst for applications in medicine, other industrialized syntheses, and

general photoredox chemistry research.

Figure 4: Three variations of pyrylium salt product were generated in mass quantities, indicative of their potential to be produced on a commercial scale: A1, A2, and A3

Figure 5: Two-step reaction scheme for pyrylium synthesis involves a chalcone

intermediate

In specific experimentation, chalcones were generated via the combination of

acetophenones and benzaldehydes (14.4mmol each) in 15mL ethanol in heat. Sodium

hydroxide (4.5ml, 4M) was added while stirring, and the solution filtered and dried. A 94.0%

yield of chalcone was achieved; it is sticky, bright white, and powdery in composition, and

chemical composition was confirmed via 1H NMR on an HNMR Ready 60 Pro. 5.6mmol of

chalcone was combined with 5.4mmol acetophenone and 0.5mL of sulfuric acid; it was then

filtered and dried. A 7.7% yield of A1 pyrylium was generated. This yield was much lower, as

following recrystallization, two groups of product formed: a deep red-orange A1 pyrylium salt

(hypothesized to be a more pure catalyst and utilized in subsequent experimentation and

analysis, as well as the reported yield calculation), alongside a lighter-orange, powdery

byproduct also present (suspected to be less pure and not analyzed further). Following A1 salt

generation, a proton NMR was taken in DMSO, and other samples analyzed with three

techniques. UV-Vis spectrometry was conducted via a Vernier Spectrophotometer and

Aftermath Software upon a 16 μM solution to collect absorption and emission spectra. These

were utilized to find excited state energy. Cyclic voltammetry was carried out via a potentiostat

and CV Pine Research Software Sonicator: Branson CPX 5800H Ultrasonic Cleaner in a

sample dissolved in tetrabutylammonium hexafluorophosphate solution.1

Figure 6: The oxidation of 1-phenylethanol by Lithium nitrate was used as a test reaction for pyrylium activity

Catalytic activity was showcased through the oxidation of 1-phenylethanol by 17mg of

lithium nitrate, added to 0.05 equivalents of A1 pyrylium. 30 microliters of 1-phenylethanol

subsequently added, followed by 1mL of deuterated acetonitrile. Solution turned a very bright,

neon yellow-green. Reaction proceeded for 90 minutes under bright blue lightbox, and HMDSO

internal standard added (10 microliters). NMR was conducted in DMSO at 400 MHz via an

HNMR Ready 60 Pro.1

Figure 7: 1H NMR of chalcone

Figure 8: 1H NMR of pyrylium salt

Figure 9: 1H NMR of oxidized alcohol

References: 1.     Department of Chemistry, The University of North Carolina at Chapel Hill. Hayden-McNeil. Laboratory in Organic Chemistry [Online]. Chapel Hill, NC (accessed January 20, 2019).2.     Huff, C. A.; Cohen, R. D.; Dykstra, K. D.; Streckfuss, E.; Dirocco, D. A.; Krska, S. W. The Journal of Organic Chemistry 2016, 81 (16), 6980–6987.3.     Joshi-Pangu, A.; Lévesque, F.; Roth, H. G.; Oliver, S. F.; Campeau, L.-C.; Nicewicz, D.; Dirocco, D. A. The Journal of Organic Chemistry 2016, 81 (16), 7244–7249.4.     Parker, M. L. “Generating Power Like Plants.” 2018, 1–3.5.     Romero, N. A.; Nicewicz, D. A. Chemical Reviews 116, 10099–101046.     Gebeyehu, D. & Sariciftci, N. S.; Journal of EEA 2008, 25, 63-727. Kalyanasundaram, K.; Grätzel, M. Optoelectronic Properties of Inorganic Compounds 1999, 169–194. 8. Paweł Szlachcic, Tomasz Uchacz, Influence of fluorine on photophysical,

electrochemical properties and basicity of 1,3-diphenylpyrazolo[3,4-b]quinoline derivatives,Journal of Luminescence, Vol. 194, 2018, Pages 579-587, ISSN 0022-2313,https://doi.org/10.1016/j.jlumin.2017.09.016.