Synthesis of 4-electron-accepting carbonyl-N-methylpyridinium species for lithium-organic batteries

Summary Biologically derived redox-active motifs have great potential in energy storage due to their inherent functionality and availability from natural resources. In this protocol, we describe the synthesis and characterization of a class of bio-derived 4-electron-accepting carbonyl-N-methylpyridinium species for lithium-organic batteries. This protocol enables the synthesis of three small molecules and two conjugated polymers with carbonyl-N-methylpyridinium units in good quantities. We also detail the fabrication process and performance evaluation of the coin-cell-type lithium-organic batteries. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1


SUMMARY
Biologically derived redox-active motifs have great potential in energy storage due to their inherent functionality and availability from natural resources. In this protocol, we describe the synthesis and characterization of a class of bioderived 4-electron-accepting carbonyl-N-methylpyridinium species for lithiumorganic batteries. This protocol enables the synthesis of three small molecules and two conjugated polymers with carbonyl-N-methylpyridinium units in good quantities. We also detail the fabrication process and performance evaluation of the coin-cell-type lithium-organic batteries. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022). 1

BEFORE YOU BEGIN
Compared with the limited resources of inorganic materials, organic compounds have become an attractive alternative electrode for the next generation of lithium organic battery (LOB) because of their unique advantages such as lightweight, low-cost, flexible, environmentally friendly and structure diversity. Among them, new organic molecules that exhibit multiple and stable redox reactions, limited solubility and improved conductivity can compete with high-performance inorganic electrode materials. [2][3][4] As the key motif in NAD + /NADH couple involved in electron-transfer reaction in natural system, carbonylpyridinium redox-active unit has attracted our attention. The early basic work of Leventis et al. has proved that the benzoyl-N-methylpyridinium (BMP) part can accept two electrons per unit, and has two reversible redox events and a high theoretical capacity. 5 Sanford et al. have certificated that BMP derivatives are very promising for redox flow batteries. However, the exploration of the application of this potential biologically derived redox active structure in lithium-ion batteries is still at an early stage, mainly due to its high solubility in common electrolytes. 6 Recently, we reported a series of novel carbonylpyridinium-based small molecules and polymers with extended conjugation to solve the above issue. These materials show promising performance as organic anodes for LOB applications, and both cycling stability and rate performance are significantly enhanced through polymerization. 1 Therefore, the current protocol describes the step-by-step synthesis of the class of 4-electronaccepting carbonyl-N-methylpyridinium species (Scheme 1), with a specific focus on S3, 3 and CP2. The protocol can also be extended to the synthesis of other derivatives (S1, S2, 1, 2 and CP1). Moreover, detailed fabrication and characterization of coin-cell LOB has been described. For the same experiment performed in batch, please refer to Wang  1. Prepare a 500 mL Schlenk flask, magnetic stirrer, a 16 mm syringe (for solvent) and a 12 mm syringe (for butyllithium), a. Place them in an air-blast drying oven and dry at 110 C for 1 h. b. Quickly transfer to an exchange chamber in the glove box for vacuum cooling to 25 C. 2. Take out n-BuLi from the refrigerator 30 min in advance, allowing it warm to 25 C before use. CRITICAL: HCl is a corrosive chemical; thus, the preparation should be handled in the fume hood and the researcher should also wear protective gloves, masks and goggles.
4. Weigh 8 g NaOH into a 250 mL beaker, and add 100 mL deionized water while stirring to obtain 2 M NaOH solution.
CRITICAL: NaOH is highly corrosive and tends to absorb water from the air, so weighing should be done in beakers rather than weighing paper. During the process of dissolving NaOH, a large amount of heat is released. Please pay attention to safety. CRITICAL: 1) n-Butyllithium, Iodomethane, Bis(triphenylphosphine)palladium(II) chloride (Pd(PPh 3 ) 2 Cl 2 ) should be stored at 4 C. 2) Dry solvents, such as dry THF and dry DMF, need to be taken in a nitrogen atmosphere for use. 3) n-Butyllithium is prone to spontaneous combustion in air. Reaction systems and solvents using butyllithium should be kept strictly free of water and oxygen.

KEY RESOURCES
Alternatives: In this protocol, the dry THF could be prepared by distillation over CaH 2 .

MATERIALS AND EQUIPMENT
Note: The HCl solution can be stored at 25 C for 3 months.
Note: The NaOH solution can be stored at 25 C for one month. In this part, we take 4,4'- (3) as an example to describe the synthesis in detail. This protocol has also been extended to the synthesis of 4,4'- (2). The overall synthetic route is presented in Scheme 1. CRITICAL: A dry needle should be used to access the butyllithium and a sealing film should be wrapped around the connection between the syringe and the needle. In detail, first extend the nitrogen-passed needle above the liquid level; then aspirate the butyllithium and transfer it quickly to the reaction flask, pushing it in gradually and without venting. The whole process should preferably be completed within three minutes. An ethanol wash bottle should be prepared to clean the used needles.
h. Add 4-cyanopyridine (2.2 g, 22 mmol) dissolved in 15 mL dry THF to the reaction flask using syringe in 5 min. Allow the mixture stir at À78 C for 2 h and then warm up to 25 C slowly for a further 2 h.
Note: The reaction mixture changes from off-white to yellow, then to brown and finally to black.
i. Add 2 M HCl (80 mL) to quench the reaction, and the mixture was stirred for 2 h at 25 C. j. Basicify the mixture to pH 9-10 by adding 2 M NaOH solution (80 mL). k. Collect the solid by vacuum filtration using a Buchner funnel, wash it with H 2 O (3 3 20 mL), CH 3 OH (3 3 20 mL) and CH 2 Cl 2 (3 3 20 mL). l. Purify the product by washing with hot THF.
Note: The crude product was suspended in 100 mL THF, heated to 70 C for 4 h. After cooling down, the pure product was collected by vacuum filtration and dried in vacuo. The desired product was obtained yellow solids in 55%. Note: No well-resolved 13 C NMR spectrum of S3 could be obtained due to its extremely limited solubility.
Analytical data for S1: Yield: 86%; white solid. 1     Note: The synthesis of CP1 was similar to that used to prepare CP2, except 1,4-bis(ethynyl) benzene (63 mg, 0.5 mmol) was used in place of 4,7-diethynyl-2,1,3-benzothiadiazole. The resulting two polymers are not soluble in water, organic solvents, or organic carbonates (electrolyte), indirectly affirming their polymeric structure. The chemical structures of the polymers were verified by Fourier transform infrared spectroscopy (FTIR) and solid-state 13 C NMR spectroscopy.

Prepare three electrodes (
CRITICAL: Polish the glassy carbon disk electrode on a cloth polishing pad in a wateralumina slurry with figure-eight motions. When using circular motions, the polishing is often uneven, leading to a slanted surface. getting oxygen free signals of the analytes, nitrogen atmosphere was kept over the solution during electrochemical experiments. (Figures 1C and 1D).

Record the CV and DPN
CRITICAL: For trusted comparison, the scan rate must be kept the same. Changing the scan rates often leads to the shifts of the redox peaks.

Part 4: Assembly of Li-organic batteries
Timing: 3 days The overall preparation of the working electrodes is illustrated in Figure 2.  CRITICAL: Grind the slurry in one direction scraping solids off of the agate mortar walls and push them back to the center every five minutes before continuing to grind. CRITICAL: Make sure to fully dry the prepared working electrodes in a vacuum drying oven at 80 C for 12 h to remove any solvent residues.
f. Flatten the electrodes.
CRITICAL: Use a Manual infrared tablet press to tablet the electrodes at a pressure of 4 MPa to prevent the foam nickel wafer from penetrating the separator.
g. Calculate the mass loading.
Note: Weigh the mass of the dried electrode sheet and calculate the mass of the coated active substance. The mass loading of active material in this protocol is 0.8-1.0 mg cm -2 . Note: Foam nickel wafer pasted active materials was used as the working electrode, 1 mol/L LiPF 6 +EC/EMC/DMC (1:1:1, v/v, 1% vinyl carbonate as additive) as the electrolyte, cel-gard2400 as the separator, and lithium foil of the corresponding size as the counter electrode. These materials are commercially available and stored in glove box.
b. Assembly the coin cells.
Note: Put the positive plate, working electrolyte, separator, lithium plate, spacer (0.8 mm) and gasket into the positive shell in order, and cover the negative shell of the battery.
c. Use the battery sealing machine to pressurize the battery to $8.5 MPa for sealing. Place the assembled battery in a box and place it in a 30 C incubator for 8 h to be tested.

Part 5: Li-ion battery tests
For the characterization of the battery performance, the coin cells were connected to the LANHE CT3001A battery test system to record the galvanostatic charge/discharge behaviors, cycling performance at constant current and rate performance at different current densities. In addition, the CV and electrochemical impedance spectra were tested by an electrochemical workstation   Figure 5A). The program setting is displayed in Figure 4D. b. Record the galvanostatic charge-discharge (GCD) curves at a current density of 0.5 A g -1 (Figure 5B).
Note: Firstly discharge to 0.05 V and then charge to 3.00 V at a constant current of 0.5 A g -1 . It can also be used to test the GCD curves at other current densities.
c. Measure the long-term cycling performance at the lower current density of 0.5 A g -1 and 0.2 A g -1 (Figures 5C and 5D). The program setting is presented in Figure 4B. d. Measure the rate performance at different current densities ( Figure 5E). The program setting is displayed in Figure 4C. e. Analyze the electrochemical impedance spectroscopy (EIS).
Note: It was carried out using an electrochemical workstation (CHI760E) at a frequency range between 100 kHz to 0.1 MHz. The detailed program settings are displayed in Figure 4E.

EXPECTED OUTCOMES
This protocol provides the synthesis of a class of 4-electron-accepting carbonyl-N-methylpyridinium species, with a focus on the procedure of 3 and CP2. Other materials (1, 2 and CP1) can be obtained following the similar protocol. It also describes the detailed procedure for battery assembly and analysis of the battery performance. The designed molecular compounds 1-3 can reversibly store up to four electrons, which is highly beneficial to increase the charge-storage capacity in battery. Both cycling stability and rate performance are further enhanced through polymerization, as a result of high electrochemical activity and effective suppression of dissolution. Impressively, polymer CP2 delivers not only the highest capacity but also the best cycling stability, reaching up to 574 mAh g -1 after 400 cycles at 0.5 A g -1 , and even as high as 807 mAh g -1 after 300 cycles at 0.2 A g -1 .

LIMITATIONS
There are several limitations to this protocol. First, n-butyllithium is extremely sensitive to water. When using it for synthesis, it is necessary to ensure that the reaction solvents and glassware used are dried; otherwise the yield of the reaction will be low. Secondly, the quality of polymers may slightly vary from different batches, and therefore strictly keep the reaction conditions as same is important. If available, we would recommend to synthesize polymers in sufficient quantities at one time to ensure that all characterizations use the same batch of polymer. Thirdly, the slurry must be ground evenly when fabricating the working electrodes; otherwise the mass distribution of the active material will be uneven, resulting in a large difference in battery performance.

Problem 1
Low yield of S3 arising from air and water sensitivity of n-BuLi (step 1g in part 1: synthesis of small molecules).

Potential solution
Butyllithium is highly sensitive to water and air. Therefore, the reaction bottle, solvents and the needle for solvent transfer much be dried in advance before the experiment. We recommend using the fresh distilled tetrahydrofuran.

Problem 2
Polymerization reactions may not occur or polymer yields are low (step 3c in part 2: synthesis of conjugated polymers).

Potential solution
Remove oxygen in the solvent during the polymerization, which plays a crucial role in the occurrence and yield of the polymerization reaction. During the synthesis of conjugated polymers CP1 and CP2, the solvents are measured with help of syringes and must contain no air. It is necessary to remove the air inside by bubbling the solvent-filled syringe for 2 min before injection.

Problem 3
Different batches of polymers may lead to differences in cell performance due to differences in polymerization (part 2: synthesis of conjugated polymers).

Potential solution
Because of the variation in compounds synthesized from batch to batch, we need to synthesize enough polymers for all characterizations at once to ensure that the same batch is used for all characterizations.

Problem 4
Spurious peaks may appear during the CV test (part 3: measurement of electrochemistry).

Potential solution
Oxygen is electroactive and can be reduced quite easily, interfering with the CV testing. Before measuring the reduction processes for 1-3 by CV, it is better to bubbling an inter gas (e.g., N 2 ) through the solution for about 2 min.

Problem 5
There are differences in the electrochemical properties of cells made from the same batch (part 4: assembly of Li-organic batteries and part 5: Li-ion battery tests).

Potential solution
In the process of making battery cathode sheets, the unevenness of the ground slurry may lead to differences in battery performance. Care should be taken to always grind in one direction throughout the process of grinding the slurry. Also, scrape it to the bottom of the mortar after every five minutes of grinding before continuing to grind. In the process of grinding the active material and carbon black, it should be ground for at least 30 min to ensure full contact between the active material and carbon black. In addition, differences mass loading of active material pasted onto the foam nickel wafer can lead to differences in battery performance. The best approach is to apply a uniform coating and select working electrodes with a similar mass of mass loading of active material (difference of no more than 0.05 mg) for the fabrication of cell.

RESOURCE AVAILABILITY
Lead contact Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Xiaoming He (xmhe@snnu.edu.cn).

Materials availability
All reagents generated in this study are available from the lead contact.

Data and code availability
No unique datasets or codes were generated in this study.