Structure of (R)-Tetrahydrofuran-3-ol
CAS No.: 86087-24-3
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Monofluorinated Cyclic Ethers Enable Fast Ion Transport in Low-Temperature Lithium Metal Batteries
Wang, Ke-Hsin ; Ma, Peiyuan ; Kim, Jaemin ; Han, Michael ; Amanchukwu, Chibueze V ;
Abstract: Lithium metal batteries (LMBs) are promising next-generation batteries because of their high energy density. To enable high lithium plating-stripping reversibility, electrolyte design is critical. State-of-the-art solvents are fluorinated linear ethers, which demonstrate good lithium metal compatibility due to the ether component and improved cathode compatibility due to fluorination. However, the fluorinated cyclic ether family, especially 3-position-functionalized tetrahydrofuran (THF), has yet to be investigated. Herein, we modified the structure of 3-methyl THF (3MTHF) through fluorination, designing electrolytes with improved lithium compatibility. Electrolytes using 3FTHF (3-fluorotetrahydrofuran) as the solvent enable 20 μm Li||LiFePO4 (LFP) full cell cycling with 80% capacity retention after 175 cycles. Moreover, the fast ion transport of this electrolyte enables it to maintain a higher capacity and better lithium plating/stripping reversibility at a current density of C/3 and −20 °C compared to 1,1,1-trifluoro-2-(2-(2,2-difluoroethoxy)ethoxy)ethane (F5DEE), one of the leading state-of-the-art electrolytes. By optimizing the physicochemical properties such as conductivity, solvation behavior, and oxidative stability, we designed a single-solvent, single-salt electrolyte with high lithium compatibility and conductivity for LMBs at ambient and low-temperature conditions.
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Keywords: cyclic ethers ; solvation ; fluorination ; low temperature ; lithium metal batteries
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CAS No. : | 86087-24-3 |
Formula : | C4H8O2 |
M.W : | 88.11 |
SMILES Code : | O[C@@H]1CCOC1 |
MDL No. : | MFCD00067101 |
InChI Key : | XDPCNPCKDGQBAN-SCSAIBSYSA-N |
Pubchem ID : | 641512 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 21.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.57 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.84 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.13 |
Solubility | 65.6 mg/ml ; 0.745 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.26 |
Solubility | 159.0 mg/ml ; 1.8 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.18 |
Solubility | 133.0 mg/ml ; 1.51 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.13 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.93 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With sodium hydride; In N,N-dimethyl-formamide; for 18h; | c. SYNTHESIS OF (R)-6-METHYL-4-((TETRAHYDROFURAN-3- YL)OXY)PICOLINONITRILE (COMPOUND 3)To a solution of (R)-tetrahydrofuran-3-ol (693 mg, 7.86 mmol, 2.0 eq) and sodium hydride (199 mg, 7.86 mmol, 2.0 eq) in DMF (20 mL) was added compound 2 (600 mg, 3.93 mmol, 1.0 eq). After 18 hours, the reaction was diluted with EtOAc and washed with water and brine twice. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 325 mg (40%) of the title compound: 1H NMR (400 MHz, , DMSO-d6) delta 7.52 (d, J = 2.28 Hz, 1H), 7.18 (d, J = 2.28 Hz, 1H), 5.22-5.19 (m, 1H), 3.91-3.33 (m, 4H), 2.46 (s, 3H), 2.34-2.25 (m, 1H), 2.00-1.93 (m, 1H); ES-MS [M+1]+: 205.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.7% | Intermediate IV andBromo-2,3-dihydro-1H-pyrrolo (2,3-b) pyridine to give d,React with (S) -3-hydroxytetrahydrofuran,A dark yellow solid VId was obtained.The intermediate d with activated carbon,Ferric chloride and hydrazine hydrate reduction,Obtained as an off-white solid VIId.Then VIId and diethyl phosphoric acid condensation,Compound VIIId is obtained,In the condensation with (dimethylamino) acetaldehyde diethyl acetal,The target compound was obtained. Yield: 48.7percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54.54% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; | To a stirred solution of <strong>[22717-55-1]methyl 4-chloro-2-hydroxybenzoate</strong> (2.0 g, 10.718 mmol, 1.05 eq) in THF (20 mL) was added (R)-tetrahydrofuran-3-ol (1.88 g, 21.437 mmol, 2.0 eq)followed by triphenylphosphine (5.62 g, 21.437 mmol, 2.0 eq) and diethylazodicarboxylate(5.04 g, 28.940 mmol, 2.7 eq). The reaction mixture was stirred at room temperature forovernight. After completion of the reaction (monitored by TLC), the reaction mixture wasdiluted with EtOAc (200 mL) and washed with water (100 mL). The organic layer was dried10 over Na2S04, filtered and evaporated under reduced pressure. The residue was purified bysilica gel column chromatography by using 0-20% ethyl acetate in hexane gradient. Thefractions containing the expected product were combined and concentrated under reducedpressure to obtain the title compound ( 1.5 g, yield: 54.54%) as a colourless liquid. 1 H NMR(300 MHz, CDCh): 8 ppm 7.76 (d, J = 8.4 Hz, lH), 6.98 (dd, J = 8.4, 1.8 Hz, lH), 6.88 (d, J15 = 1.8 Hz, lH), 5.0-4.93 (m, lH), 4.10-3.85 (m, 7H), 2.24-2.17 (m, 2H); ESI-MS: m/z 256.91(M+Ht. |
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