Reaction of Amphipathic-Type
Thioester and Amine with Hydrophobic Effect in Water

Atsushi Torihata; Chiaki Kuroda

doi:10.1055/s-0030-1261165

LETTER

Reaction of Amphipathic-Type Thioester and Amine with Hydrophobic Effect in Water

Atsushi Torihata, Chiaki Kuroda*
Department of Chemistry and Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Fax: +81(3)39852396; e-Mail: chkkuroda@grp.rikkyo.ne.jp;

Abstract

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Abstract

The title reaction was studied using sodium 3-(1-oxododec-1-yl)thio- and 3-(1-oxohept-1-yl)thiopropanoate with various chain lengths of amines. The yields of the amides were found to depend on both the chain length of the thioester and that of amine, suggesting the presence of hydrophobic interaction. The amides were obtained in better yields after addition of sodium fluoride. Acylation (dodecanoylation) of some hydrophobic amino acids was also studied to obtain the corresponding amides.

Key words

amines - amides - amino acids - thioesters - hydrophobic effect

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References

References and Notes

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Compound 7: IR (KBr): 1684, 1566, 1425 cm^-¹. ^¹H NMR as carboxylic acid (CDCl₃): δ = 0.88 (t, J = 6.4 Hz, 3 H), 1.21-1.37 (m, 6 H), 1.59-1.70 (m, 2 H), 2.55 (t, J = 7.5 Hz, 2 H), 2.69 (t, J = 6.9 Hz, 2 H), 3.11 (t, J = 6.9 Hz, 2 H). ^¹³C NMR as carboxylic acid (CDCl₃): δ = 14.0, 22.4, 23.5, 25.5, 28.6, 31.4, 34.2, 44.0, 177.2, 199.3. MS (FAB): m/z = 263 [M + Na]⁺, 241 [M + H]⁺. HRMS (FAB): m/z [M + H]⁺ calcd for C₁₀H₁₈O₃NaS: 241.0874; found: 241.0865.

<A NAME="RU03611ST-8">8</A> Dellaria JF. Nordeen C. Swett LR. Synth. Commun. 1986, 16: 1043

Typical Procedure for the Amidation Reaction: Thioester 6 (0.065 mmol) was added to a stirred mixture of amine 3 (0.13 mmol) in H₂O (5 mL), and the mixture was stirred at r.t. for 24 h. The mixture was extracted with Et₂O, and the ethereal layer was washed with aq NaHCO₃ solution, and dried over Na₂SO₄. After evaporation of the solvent, the product was purified by silica gel column chromatography using hexane-EtOAc as eluent.

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An aqueous solution of NaOH (0.5 M, 0.26 mL) was added in the reaction of 8 triflate (0.13 mmol) with 6 (0.065 mmol).

Compound 9a: mp 60-61 ˚C. IR (KBr): 3315, 1739, 1647, 1552, 1213 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 7.0 Hz, 3 H), 0.89 (t, J = 7.0 Hz, 3 H), 1.23-1.39 (m, 22 H), 1.55-1.69 (m, 4 H), 2.24 (t, J = 7.4 Hz, 2 H), 4.04 (d, J = 5.0 Hz, 2 H), 4.15 (t, J = 6.7 Hz, 2 H), 5.94 (br, 1 H). ^¹³C NMR (CDCl₃): δ = 14.0, 14.1, 22.5, 22.7, 25.4, 25.6, 28.4, 29.2, 29.3 (2 × C), 29.4, 29.6 (2 × C), 31.3, 31.9, 36.4, 41.3, 65.7, 170.3, 173.2. EIMS: m/z = 341 [M⁺], 201, 118. HRMS: m/z [M + H]⁺ calcd for C₂₀H₄₀NO₃: 342.3008; found: 342.3002.

Compound 9b: mp 45-46 ˚C. IR (KBr): 3296, 1732, 1639, 1552, 1186 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 6.7 Hz, 3 H), 0.89 (t, J = 6.2 Hz, 3 H), 1.22-1.37 (m, 22 H), 1.55-1.69 (m, 4 H), 2.15 (t, J = 7.5 Hz, 2 H), 2.53 (t, J = 5.9 Hz, 2 H), 3.52 (q, J = 5.9 Hz, 2 H), 4.09 (t, J = 6.8 Hz, 2 H), 6.07 (br, 1 H). ^¹³C NMR (CDCl₃): δ = 14.0, 14.1, 22.5, 22.7, 25.6, 25.7, 28.5, 29.3 (3 × C), 29.5, 29.6 (2 × C), 31.4, 31.9, 34.0, 34.7, 36.8, 173.0, 173.2. EIMS: m/z = 355 [M⁺], 215, 132. HRMS: m/z [M + H]⁺ calcd for C₂₁H₄₂NO₃: 356.3165; found: 356.3134.

Compound 11a: oil. IR (NaCl): 3307, 1736, 1651, 1539, 1198 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 6.8 Hz, 3 H), 0.89 (t, J = 6.8 Hz, 3 H), 0.90 (d, J = 7.0 Hz, 3 H), 0.94 (d,
J = 7.0 Hz, 3 H), 1.22-1.39 (m, 22 H), 1.59-1.69 (m, 4 H), 2.10-2.21 (m, 1 H), 2.23 (t, J = 7.7 Hz, 2 H), 4.07-4.18 (m, 2 H), 4.58 (dd, J = 4.6, 8.8 Hz, 1 H), 5.94 (br d, J = 9.0 Hz, 1 H). ^¹³C NMR (CDCl₃): δ = 14.0, 14.1, 17.7, 18.9, 22.5, 22.7, 25.6, 25.7, 28.5, 29.2, 29.3 (2 × C), 29.5, 29.6 (2 × C), 31.3, 31.4, 31.9, 36.8, 56.8, 65.4, 172.4, 173.0. EIMS: m/z = 383 [M⁺], 254. HRMS: m/z [M + H]⁺ calcd for C₂₃H₄₆NO₃: 384.3478; found: 384.3478.

Compound 11b: oil. IR (NaCl): 3288, 1741, 1651, 1543, 1192 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 6.8 Hz, 3 H), 0.89 (t, J = 6.8 Hz, 3 H), 0.94 (d, J = 6.3 Hz, 3 H), 0.95 (d, J = 6.0 Hz, 3 H), 1.23-1.39 (m, 23 H), 1.46-1.72 (m, 6 H), 2.21 (t, J = 7.5 Hz, 2 H), 4.12 (t, J = 5.8 Hz, 2 H), 4.65 (dt, J = 5.0, 8.7 Hz, 1 H), 5.84 (br d, J = 8.0 Hz, 1 H). ^¹³C NMR (CDCl₃): δ = 14.0, 14.1, 22.1, 22.5, 22.7, 22.8, 24.9, 25.5, 25.6, 28.4, 29.2, 29.3 (2 × C), 29.5, 29.6 (2 × C), 31.3, 31.9, 36.6, 41.9, 50.6, 65.5, 172.8, 173.4. EIMS: m/z = 397 [M⁺], 268, 86. HRMS: m/z [M + H]⁺ calcd for C₂₄H₄₈NO₃: 398.3634; found: 398.3616.

Compound 11c: oil. IR (NaCl): 3300, 1738, 1653, 1537, 1192 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 6.9 Hz, 3 H), 0.89 (t, J = 6.8 Hz, 3 H), 0.90 (d, J = 6.8 Hz, 3 H), 0.93 (t,
J = 7.2 Hz, 3 H), 1.22-1.40 (m, 24 H), 1.58-1.72 (m, 4 H), 1.83-1.94 (m, 1 H), 2.22 (t, J = 7.6 Hz, 2 H), 4.11 (dt, J = 10.7, 6.7 Hz, 1 H), 4.14 (dt, J = 10.7, 6.7 Hz, 1 H), 4.62 (dd, J = 4.6, 8.5 Hz, 1 H), 5.97 (br d, J = 8.5 Hz, 1 H). ^¹³C NMR (CDCl₃): δ = 11.6, 14.0, 14.1, 15.4, 22.5, 22.7, 25.2, 25.5, 25.7, 28.5, 29.2, 29.3 (2 × C), 29.5, 29.6 (2 × C), 31.3, 31.9, 36.8, 38.1, 56.1, 65.4, 172.3, 172.8. EIMS: m/z = 397 [M⁺], 268, 86. HRMS: m/z [M + H]⁺ calcd for C₂₄H₄₈NO₃: 398.3634; found: 398.3647.

Compound 11d: mp 45-46 ˚C. IR (KBr): 3326, 1732, 1645, 1523, 1209 cm^-¹. ^¹H NMR (CDCl₃): δ = 0.88 (t, J = 6.6 Hz, 3 H), 0.90 (t, J = 6.0 Hz, 3 H), 1.23-1.38 (m, 22 H), 1.52-1.68 (m, 4 H), 2.17 (t, J = 7.6 Hz, 2 H), 3.11 (dd, J = 5.8, 14.0 Hz, 1 H), 3.14 (dd, J = 6.0, 14.0 Hz, 1 H), 4.04-4.15 (m, 2 H), 4.90 (dt, J = 7.7, 6.0 Hz, 1 H), 5.90 (br d, J = 8.0 Hz, 1 H), 7.08-7.34 (m, 5 H). ^¹³C NMR (CDCl₃): δ = 14.0, 14.1, 22.5, 22.7, 25.5, 25.6, 28.4, 29.2, 29.3 (2 × C), 29.4, 29.6 (2 × C), 31.3, 31.9, 36.6, 38.0, 52.9, 65.7, 127.0, 128.5 (2 × C), 129.3 (2 × C), 136.0, 171.8, 172.6. EIMS: m/z = 431 [M⁺], 232, 120. HRMS: m/z [M + H]⁺ calcd for C₂₇H₄₆NO₃: 432.3478; found: 432.3491.