Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework

Summary

Here, we present a one-pot, transition-metal-free synthesis of thiols and thioesters from aromatic halides and sodium thiomethoxide, followed by the preparation of single crystals of a metal-dithiolene network using thiol species generated in situ from the more stable and tractable thioester.

Abstract

We present a method for preparing thioester molecules as the masked form of the thiol linkers and their utilization for accessing a semiconducting and porous metal-dithiolene network in the highly ordered single crystalline state. Unlike the highly reactive free-standing thiols, which tend to decompose and complicate the crystallization of metal-thiolate open frameworks, the thioester reacts in situ to provide the thiol species, serving to mitigate the reaction between the mercaptan units and the metal centers, and to improve crystallization consequently. Specifically, the thioester was synthesized in a one-pot procedure: an aromatic bromide (hexabromotriphenylene) reacted with excess sodium thiomethoxide under vigorous conditions to first form the thioether intermediate product. The thioether was then demethylated by the excess thiomethoxide to provide the thiolate anion that was acylated to form the thioester product. The thioester was conveniently purified by standard column chromatography, and then used directly in the framework synthesis, wherein NaOH and ethylenediamine serve to revert in situ the thioester to the thiol linker for assembling the single-crystalline Pb(II)-dithiolene network. Compared with other methods for thiol synthesis (e.g., by cleaving alkyl thioether using sodium metal and liquid ammonia), the thioester synthesis here uses simple conditions and economical reagents. Moreover, the thioester product is stable and can be conveniently handled and stored. More importantly, in contrast to the generic difficulty in accessing crystalline metal-thiolate open frameworks, we demonstrate that using the thioester for in situ formation of the thiol linker greatly improves the crystallinity of the solid-state product. We intend to encourage broader research efforts on the technologically important metal-sulfur frameworks by disclosing the synthetic protocol for the thioester as well as the crystalline framework solid.

Introduction

There is currently great interest in employing strong, polarizable metal-sulfur (e.g., metal-thiolate) links for constructing open framework materials with enhanced electrocatalytic and conductive properties^{1,2,3,4,5,6,7,8,9,10}. In addition to promoting electronic interaction and transport in the extended state, the soft and covalent metal-sulfur links also impart better stability for applications in aqueous environments. Among the sulfur-equipped building blocks, symmetrical, multidentate polycyclic aromatic building blocks like 2,3,6,7,10,11-triphenylene hexathiol (HTT)^{9,11,12,13,14} not only supply highly polarizable π-electrons, but also offer distinct advantages with respect to framework design and synthesis. First, the rigid and symmetrical triphenylene core, in conjunction with the chelating dithiolene groups of HTT, serves to lock in metal ions in regular bonding motifs, simplifying the structural prediction of the prospective network^7,15. Together with the rigid and open geometry of the sulfur linker, framework structures with substantial porosity features can often be achieved in the solid state.

One major challenge in assembling thiol-equipped metal orangic framework (MOF) materials is rooted in the synthesis of the organic linker molecules. In a classical protocol, the thiol group had to be derived from the phenol group using the Newman-Kwart rearrangement of the O-aryl thiocarbamate precursor^16,17,18. This approach, however, involves elaborate preparative steps for the phenol precursor molecule as well as potential complications of a high-temperature solid phase transformation. Another way of making thiols utilizes reductive dealkylation of thioethers under the harsh conditions of, for example, sodium metal in liquid ammonia^19,20,21,22, and is not compatible with the carboxyl and many other donor functions for network construction.

By comparison, the protocol presented here has multiple advantages: safety, convenience, cost-effectiveness, and compatibility with other functional groups (e.g., carbonitrile and pyridinyl). By vigorously heating the generally inexpensive aromatic halide (e.g., hexabromotriphenylene) and thiomethoxide anion, the thiolate anion was generated (via the methyl thioether intermediate product) and then acylated to give the stable and easy-to-handle thioester product-all in one pot.

We will also describe a procedure for utilizing the thioester molecules as the masked form of the thiol linkers for accessing a single-crystalline semiconducting and porous metal-dithiolene network. Unlike the highly reactive free-standing thiols, which tend to decompose and complicate the crystallization of metal-thiolate open frameworks, the thioester can be readily cleaved (e.g., by NaOH or ethylenediamine) in situ to provide the thiol species, serving to mitigate the reaction between the mercaptan units and the metal centers, and to consequently improve the crystallization.

This protocol of preparing thiol/thioester has not been widely used by other groups for the emerging field of metal-sulfur frameworks, even though nucleophilic dealkylations of alkyl aryl thioethers by thiolate anions have already been well documented by organic chemists^23,24,25,26. By showcasing this efficient synthetic method for thioesters and their use for facilitating the crystallization of metal-sulfur networks, we wish to promote further efforts to bridge the intellectual and practical divide between synthetic organic chemistry and solid state chemistry, so as to help the speedy and healthy development of porous frameworks.

Protocol

Caution: Please consult all relevant material safety data sheets before use. Methyl disulfide and sodium thiomethoxide are strongly malodorous and should be handled in a fume hood. Sodium metal is highly reactive and requires special safety precautions against potential fire and explosion hazards. In addition to the use of a fume hood, personal protective equipment (safety glasses, gloves, lab coat, full length pants, and closed-toe shoes) should be properly employed. Portions of the following procedures involve standard, air-free handling techniques.

1. Preparation of Sodium Thiomethoxide (CH₃SNa)

1. Connect a 200-mL Schlenk flask to a vacuum gas manifold. Evacuate the flask and then backfill it with N₂ three times, such that the flask is filled with a slightly positive N₂ pressure.
   NOTE: A similar method of preparing CH₃SNa was mentioned briefly in the literature, but no detailed procedures were provided^27,28.
2. Take out a block of metallic sodium from the kerosene oil reservoir. Use a paper towel to wipe off the residual oil on the surface, and use a knife to scrape off the oxide layer on the surface. Quickly cut 6.7 g of the metallic sodium (0.29 mol) into small pieces (e.g., about soybean size) and immediately transfer the small pieces to the 200-mL Schlenk flask under a counter flow of N₂. Seal the flask with a septum immediately.
   NOTE: To reduce the exposure to air, one can cut out the sodium with some variation from the amount of 6.7 g, and adjust the amounts of THF and dimethyl disulfide according to the actual amount of sodium used.
3. Transfer 80 mL of an anhydrous, airless THF into the flask via cannula under N₂ protection from the Schlenk line. Withdraw 14.0 mL of dimethyl disulfide (0.158 moles; pre-purged with N₂) into a syringe and inject it into the flask dropwise under N₂ protection.
   Caution: Dimethyl disulfide is malodorous and should be handled in a fume hood.
4. Replace the septum with a ground glass stopper. Stir the reaction mixture at room temperature for 24 h and then at 60 °C for 3 h.
   NOTE: The reaction mixture became viscous while stirring at room temperature; when heated up to 60 °C, the mixture can be stirred more easily and thus speed up the reaction towards completion.
5. With the temperature maintained at about 60 °C, use a stream of N₂ (0.2 L/min) to blow off the majority of the THF solvent and the excess dimethyl disulfide, until a dry solid appears. Use a cold trap (e.g., acetone/dry ice) to collect the THF and dimethyl disulfide in the outflow.
6. Evacuate the remaining solid mixture with an oil pump for about 2 h to remove the residual THF and dimethyl disulfide and then backfill it with N₂ to obtain a light-yellow solid (19.8 g, 97%). Store the solid product CH₃SNa in a nitrogen atmosphere in the dark.
   NOTE: To protect the vacuum oil pump, a cold trap should be used during the pumping.

2. Preparation of 2,3,6,7,10,11-hexakis(pentanoylthio)triphenylene (HVaTT) as a protected thiol linker

1. Load 0.664 g of CH₃SNa (9.0 mmol) into a 50-mL Schlenk flask under a counter flow of N₂ (i.e., connected as above to a vacuum gas manifold under N₂ protection).
   NOTE: CH₃SNa is sensitive to air and easily absorbs water. To minimize exposure to air, one can quickly weigh out a specific amount and add it to the flask, and then adjust the quantity of the other reactant, 2,3,6,7,10,11-hexabromotriphenylene (HBT), accordingly.
   Caution: Solid CH₃SNa has a strong smell and should be handled in a fume hood.
2. Add 0.216 g of HBT (0.30 mmol) to the flask under a counter flow of N₂, and seal the flask with a septum.
3. Transfer 10 mL of anhydrous and airless 1,3-dimethyl-2-imidazolidinone (DMEU) into the flask via cannula under N₂ protection from the Schlenk line.
4. Replace the septum with a regular glass stopper, and stir the reaction mixture and use a salt bath to heat it to 240 °C for 48 h under N₂.
5. TLC monitoring of the progress of the reaction: Under N₂, use a glass dropper to withdraw a small aliquot of the reaction mixture (about 0.1 mL) and immediately inject it into a neat liquid sample of valeroyl chloride (about 0.1 mL) in a plastic microcentrifuge vial, and then shake for 1 min; the mixture should immediately turn turbid with a grey-white color. Add 0.4 mL of deionized water and 0.1 mL of ethyl acetate, close the cap, and shake it for a few seconds.
   NOTE: If the reaction has completed already, there will not be anything that appears between the layers of water and ethyl acetate. If not, a white insoluble substance will appear between the two layers.
6. Pipet out the upper portion and use it for spotting the TLC plates. Use 1:4 ethyl acetate/petroleum ether to develop the TLC plate. For a complete reaction, the target molecule shows up as a regular spot around R_f = 0.4 under a UV lamp.
7. Turn off the heating and take the reaction flask out of the salt bath to cool it to room temperature, and then use an ice bath to cool the flask down to 0 °C.
8. Inject 1.5 mL of valeroyl chloride (12.6 mmol) into the flask dropwise (over a period of about 2 min) with a syringe under N₂. Keep stirring at 0 °C for 2 h. Note: adding valeroyl chloride slowly and at low temperature helps to reduce the generation of by-products.
9. Pour the mixture into 50 mL of ice water and extract using ethyl acetate (3 30 mL). Then wash the combined organic layer with water (6 60 mL), dry over anhydrous MgSO₄, and remove the volatiles by a rotary evaporator.
10. Isolate the oily crude product by column chromatography using 1:10 ethyl acetate/petroleum ether as the eluent, which affords a light-yellow oily product after rotary evaporation of the solvents. Use 1:4 ethyl acetate/petroleum ether to develop the TLC plate, R_f = 0.4. Further purify the oily product using the trituration step below.
11. Add 5 mL of methanolto the oily product, and sonicate for 2 min. Collect the resultant off-white solid using suction filtration (yield: 59%).

3. Preparation of Single Crystals of the HTT-Pb Framework Material

1. Mix 11.4 mg of PbOAc·3H₂O (0.030 mmol) in 1.0 mL of ethylene diamine in a vial to make a clear solution.
2. Load 9.1 mg of HVaTT (0.010 mmol), 2.0 mL of pre-degassed methanol solution of NaOH (70 mmol/L), and 1.0 mL of ethylene diamine into an empty 10-mL vial and sonicate for 5 min.
3. Add the PbOAc solution to the sonicated HVaTT mixture. Then bubble the reaction mixture with N₂ for 1 min, and put on the screw cap to seal the vial.
4. Heat the vial at 90 °C in an oven for 48 h, followed by natural cooling to room temperature, during which yellow-orange, octahedral single crystals suitable for single-crystal X-ray diffraction studies were formed (yield: 45%).
5. Suction filtration off the crystals and quickly wash with MeOH. Transfer the crystals with a glass dropper into a vial containing airless MeOH (5 mL) for storage at room temperature.

4. Interaction of Paraquat Diiodide with HTT-Pb Crystals

1. Use a glass Pasteur pipet to withdraw a few grains of the HTT-Pb single crystal from the MeOH stock and drop it onto a Petri dish (diameter 35 mm and depth 10 mm). Soak up the methanol liquid by tissue or filter paper (or let the MeOH dry up naturally), and then drop onto the crystals a few drops of an aqueous solution of paraquat diiodide (0.1%, w/w).
2. Observe the color change of the crystals by eye or under a microscope.

Results

The IR spectrum of the HVaTT molecule (collected by the KBr pellet method) features its strongest absorption at 1,700 cm^-1, in accordance with the carbonyl stretching of the thioester functional group. The ¹H-NMR spectrum of HVaTT (400 MHz, CDCl₃) reveals a singlet at δ 8.47 from the aromatic hydrogens, together with 4 multiplets from the aliphatic protons: δ 8.47 (s, 6H, CHAr), 2.75 -2.72 (t, J = 7.4, 12H, CH₂), 1.81-1.77 (m,...

Discussion

The reaction between the bromo group and the thiomethoxide anion apparently first produced the methyl thioether, which was then demethylated by the excess thiomethoxide to provide the thiolate anion product. To ensure complete conversion to the desired thiolate anion (especially for a polybromide substrate like HBT), the vigorous conditions of prolonged heating (e.g., 240 °C over 48 h) with a large excess of sodium thiomethoxide (e.g., over three times the moles of the bromo groups) are essential. ...

Materials

Name	Company	Catalog Number	Comments
Bromine	DAMAO CHEMICAL REAGENT FACTORY	7726-95-6	Highly toxic
Triphenylene	HWRK Chem	HWG45510
Iron powder	Sigma-Aldrich	12310
Nitrobenzene	DAMAO CHEMICAL REAGENT FACTORY	2934
Diethyl ether	DAMAO CHEMICAL REAGENT FACTORY	48
Dichloromethane	DAMAO CHEMICAL REAGENT FACTORY	3067
Sodium metal	J&K	WM-NMS-54-25X-50G	Air sensitive
Tetrahydrofuran	J&K	315353
Dimethyl disulfide	INTERNATIONAL LABORATORY USA	726415
1,3-Dimethyl-2-imadazolidinone	J&K	50483	Dried over 4Å sieves
Valeryl  chloride	J&K	99590
Methanol	Guangzhou Chemical Reagent Factory	2334
Sodium hydroxide	Guangzhou Chemical Reagent Factory	1588
Ethylene diamine	Riedel-de Haën	15070
Lead acetate trihydrate	PEKING CHEMICAL WORKE	861218