Novel l-Tartaric Acid Derived Pyrrolidinium Cations for the Synthesis of Chiral Ionic Liquids

Abstract

Novel pyrrolidinium salts based on l-(+)-tartaric acid were designed and synthesized in very good yields with a simple and practical strategy. Twelve new chiral ionic potential task-­specific catalysts, two of which are room-temperature chiral ionic liquids (RTCIL), were obtained, and their properties are discussed.

Key words

chiral pool - green solvents - ionic liquid - microwaves - chiral molecular recognition

References and Notes

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10

(3 R ,4 R )-1-Benzyl-3,4-dihydroxy-2,5-pyrrolidinedione (13)
Benzylamine (11 mL, 100 mmol) were added to a 250 mL round-bottom flask containing a suspension of l-(+)-tartaric acid (15.0 g, 100 mmol) in xylene (80 mL). The mixture was refluxed in a Dean-Stark apparatus for 4 h, and H₂O (3.6 mL, 200 mmol) was collected. Then the solid was filtered off, washed with acetone, and recrystallized from EtOH (12.5 g, 57 mmol, 57%).
(3 S ,4 S )-1-Benzyl-3,4-pyrrolidinediol (14)
To a cooled (0 ˚C) suspension of LiAlH₄ (2.28 g, 60 mmol) in dry THF (100 mL) in a 500 mL round-bottom flask the pyrrolidinedione 13 (4.42 g, 20 mmol) was added portionwise, and the mixture was heated at reflux for 12 h. The mixture was then cooled to 0 ˚C, and a sat. solution of Na₂SO₄ was added until no gas evolution was observed, then additional anhyd Na₂SO₄ was added, and the mixture was filtered through Celite washing with EtOAc. Evaporation of the solvent yielded a white solid (1.97 g, 10.2 mmol, 51%). Spectral data were identical to those reported in the literature, see ref. 9.

11

This two-step procedure has been reported to give higher yields. However, in our hands, these yields were not reproducible, and we introduced some slight modifications to render the synthesis reliable when extended to a multigram scale.

12

General Procedure for Quaternization under Conventional Heating
In a round-bottom flask the pyrrolidinediol 14 and alkyl or benzyl bromide (1.5 equiv) were suspended in MeCN. The mixture was heated at 90 ˚C until disappearance of the starting material (TLC control). The reaction mixture was cooled at 0 ˚C, and Et₂O was added to crystallize the pure product as a white solid.
General Procedure for Quaternization under Microwave Heating
In a microwave reactor, the pyrrolidinediol 14 and alkyl or benzyl bromide (1.5 equiv) were suspended in MeCN. The reaction was carried out at 90 ˚C, 150 W for 10 min (TLC control), then the reaction mixture was cooled to 0 ˚C, and the pure product crystallizes as a white solid.

15

Crystal Data for 1
MW = 364.3, trigonal, space group P31, Z = 3, D _c = 1.46, a = b = 10.686 (1) Å, c = 12.580 (1) Å, α = β = 90˚, γ = 120˚, V = 1244.1 (2) Å^³. The X-ray CIF file for this structure has been deposited at the Cambridge Crystallographic Data Centre (CCDC), deposition number 710820.

16

Crystal Data for 5
MW = 544.5, orthorhombic, space group P212121, Z = 4, D _c = 1.37, a = 9.767 (1) Å, b = 9.805 (1) Å, c = 27.605 (1) Å, α = β = γ = 90˚, V = 2643.6 (4) Å^³. The X-ray CIF file for this structure has been deposited at the CCDC, deposition number 710821.

17

Anion Exchange (Procedure A)
In a round-bottom flask the pyrrolidinium bromide 1 or 5
(1-5 mmol) were suspended in H₂O-EtOAc (1:1), then the appropriate potassium or lithium salt was added. After 5 min the two phases became limpid, and the reaction was finished. The organic phase was separated and dried with anhyd Na₂SO₄. Solvent evaporation gave the pure product.

18

Upon addition of a slight excess of AgNO₃ the solution became yellow due to formation of Ag₂CrO₄.

19

Anion Exchange (Procedure B) In a round-bottom flask the pyrrolidinium bromide 9 was suspended in H₂O, then the appropriate potassium or lithium salt was added. The mixture was left to react overnight at r.t., and the formation of a pale yellow oil, insoluble in H₂O, was observed. Ethyl acetate was then added. The organic phase was separated and dried with anhyd Na₂SO₄. Solvent evaporation gave the pure product.

20

Data for Ionic Liquid 8
Pale yellow viscous liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 7.47-7.43 (m, 10 H), 7.35-7.32 (m, 6 H), 7.22-7.19 (m, 4 H), 4.73 (A part of an AB system, J = 13.1 Hz, 2 H), 4.63 (B part of an AB system, J = 13.1 Hz, 2 H), 4.46 (A part of an AB system, J = 11.9 Hz, 2 H), 4.42 (B part of an AB system, J = 11.9 Hz, 2 H), 4.24 (br s, 2 H), 3.85 (dd, J = 13.5, 5.6 Hz, 2 H), 3.71 (dd, J = 13.5, 2.6 Hz, 2 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 135.9 (s, 2 C), 133.3 (d, 4 C), 131.0 (d, 2 C), 129.4 (d, 4 C), 128.5 (d, 4 C), 128.3 (d, 2 C), 127.9 (d, 4 C), 126.6 (s, 2 C), 119.9 (q, 2 C, CF₃, J = 319.9 Hz), 80.2 (d, 2 C), 72.3 (t, 2 C), 66.9 (t, 2 C), 60.8 (t, 2 C). ^¹9F NMR (188 MHz, acetone-d ₆,): δ = -79.9 (s). IR (CDCl₃): 3090 (w), 3068 (m), 3034 (m), 2923 (w), 2872 (w), 2260 (m), 1497 (m), 1456 (s), 1350 (s), 1199 (s), 1134 (s), 1059 (s) cm^-¹. MS: m/z (%) = 464 (0.4), 160 (9), 120 (19), 91 (100), 69 (46), 41 (52). Anal. Calcd for C₃₄H₃₄F₆N₂O₆S₂: C, 54.83; H, 4.60; N, 3.76. Found: C, 54.82; H, 4.86; N, 3.86. [α]_D ^²³ +0.9 (c 1.00, CH₂Cl₂).

21

Data for Ionic Liquid 12
Pale yellow viscous liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 7.51-7.41 (m, 5 H), 4.66-4.53 (m, 4 H), 4.17 (br s, 1 H), 4.09 (dd, J = 13.1, 4.0 Hz, 1 H), 3.98 (br s, 1 H), 3.79 (d, J = 12.8 Hz, 1 H), 3.73 (dd, J = 12.8, 4.0 Hz, 1 H), 3.37 (d, J = 13.1 Hz, 1 H), 3.30-3.15 (m, 2 H), 1.95-1.84 (m, 2 H), 1.32-1.25 (m, 18 H), 0.87 (t, J = 6.8 Hz, 3 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 132.1 (d, 2 C), 130.9 (d, 1 C), 129.4 (d, 2 C), 127.4 (s, 1 C), 119.5 (q, 2 C, CF₃, J = 318.7 Hz), 75.8 (d, 1 C), 75.5 (d, 1 C), 68.6 (t, 1 C), 67.7 (t, 1 C), 66.9 (t, 1 C), 63.8 (t, 1 C), 31.9 (t, 1 C), 29.6 (t, 2 C), 29.5 (t, 1 C), 29.4 (t, 1 C), 29.3 (t, 1 C), 29.0 (t, 1 C), 26.2 (t, 1 C), 23.7 (t, 1 C), 22.8 (t, 1 C), 14.2 (q, 1 C). ^¹9F NMR (188 MHz, acetone-d ₆): δ =
-79.8 (s, 6 F). IR (CHCl₃): 3507 (m), 3033 (w), 2927 (m), 2855 (w), 1457 (w), 1349 (s), 1192 (s), 1133 (m), 1059 (m) cm^-¹. MS: m/z (%) = 362 (35), 288 (12), 270 (11), 206 (6), 193 (7), 134 (5), 116 (100), 91 (45), 69 (11), 55 (15). Anal. Calcd for C₂₅H₄₀F₆N₂O₆S₂: C, 46.72; H, 6.27; N, 4.36. Found: C, 46.70; H, 6.55; N, 4.35. [α]_D ^²² -5.1 (c 0.985, MeOH).

22

Data for Ionic Liquid 4
Pale yellow solid; mp 50-53 ˚C. ^¹H NMR (200 MHz, CD₃OD): δ = 7.63-7.50 (m, 10 H), 4.89 (br s, 2 H), 4.71 (br s, 2 H), 4.32-4.24 (m, 2 H), 3.87 (dd, J = 12.5, 5.1 Hz, 2 H), 3.60 (dd, J = 13.2, 1.5 Hz, 2 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 133.2 (d, 4 C), 131.1 (d, 2 C), 129.5 (d, 4 C), 127.1 (s, 2 C), 119.6 (q, 2 C, CF₃, J = 320.5 Hz), 76.1 (d, 2 C), 67.4 (t, 2 C), 63.3 (t, 2 C). ^¹9F NMR (188 MHz, acetone-d ₆): δ =
-79.9 (s). IR (CH₂Cl₂): 3593 (w), 3502 (m), 3059 (w), 3032 (w), 2923 (w), 1494 (w), 1457 (w), 1351 (s), 1199 (s), 1134 (m), 1060 (m) cm^-¹. MS: m/z (%) = 284 (22), 210 (7), 193 (6), 133 (11), 120 (11), 91 (100), 65 (25), 51 (7). Anal. Calcd for C₂₀H₂₂F₆N₂O₆S₂: C, 42.55; H, 3.93; N, 4.96. Found: C, 42.36; H, 4.12; N, 4.95. [α]_D ^²³ -24.5 (c 1.01, CH₂Cl₂).