Synlett 2002(8): 1347-1349
DOI: 10.1055/s-2002-32957
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Protocol for a One-pot Synthesis of α-Amino Phosphonates by Reaction of Imines Prepared In Situ with Trialkylphosphites

Mohammad R. Saidi*, Najmedin Azizi
Department of Chemistry, Sharif University of Technology, P. O. Box 11365-9516 Tehran, Iran
Fax: +98(21)6012983; e-Mail: saidi@sharif.edu;
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Publikationsverlauf

Received 23 May 2002
Publikationsdatum:
25. Juli 2002 (online)

Abstract

Imines prepared in situ by reaction of aldehydes and ketones with primary amines in ethereal solution of LiClO4 react readily at ambient temperature with trialkylphosphite to give high yields of α-amino phosphonates.

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General Procedure for the Preparation of α-Amino Phosphonates 4. The aldehyde (2 mmol)and 4 mL of 5 M LiClO4 in diethyl ether were placed in a 50 mL flask under argon and stirred for 5 min. Then a primary amine
(3.0 mmol) and TMSCl (2.0 mmol) were added via a syringe. After 10 min, trimethyl-phosphite or triethyl-phosphite (2.5 mmol) was added and the mixture was stirred at r.t. for about 15 min. Then water (20 mL) and CH2Cl2 (20 mL) were added. The organic phase was separated, dried over MgSO4, and the solvent was removed. Almost pure crude product obtained. Further purification was carried out by column chromatography on basic alumina eluting with petroleum ether/EtOAc, if needed. All compounds were characterized on the basis of spectroscopic data (IR, NMR, MS) and comparison with those reported in the literature. Caution: Although we did not have any accident while using LiClO4, it is advisable to dry lithium perchlorate in a fume hood using a suitable lab-shield.

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Selected spectral data. 4a: IR (KBr): 3304 cm-1 (NH).
1H NMR (CDCl3, 500 MHz): δ = 3.48 (d, 3 H, J = 6.1 Hz), 3.78 (d, 3 H, J = 10.7 Hz), 4.50 (br s, 1H, NH), 4.83 (d, 1 H, J = 24.3), 6.61-6.72 (m, 3 H), 7.28-7.50 (m, 7 H). 13C NMR (CDCl3, 125 MHz): δ = 53.68 (d, ² J PC = 6.6 Hz), 54.2 (d, ² J PC = 7.6 Hz), 55.6 (d, ¹ J PC = 150.6 Hz), 114.2, 119.2, 123.4, 129.0, 129.8 (d, J PC = 4.5 Hz), 130.2, 135.9 (d, J PC = 2.5 Hz), 146.4 (d, J PC = 14.7 Hz). 4c: IR (KBr): 3314 cm-1 (NH). 1H NMR (CDCl3, 500 MHz): δ = 3.55 (d, 3 H, J = 10.6 Hz), 3.78 (d, 3 H, J = 10.7), 4.83 (d, 1 H, J = 24.6 Hz), 4.85 (br s, 1 H, NH), 6.62-7.46 (m, 9 H). 13C NMR (CDCl3, 125 MHz): δ = 53.70 (d, ² J PC = 6.6 Hz), 54.2 (d, ² J PC = 6.0 Hz) 55.02 (d, ¹ J PC = 154 Hz), 114.0, 119.1, 129.0, 129.6 (d, J PC = 8.1), 129.9, 130.2, 134.2 (d, J PC = 3.9 Hz), 146.4 (d, J PC = 15.0 Hz). 4g: IR (KBr): 3325 cm-1 (NH). 1H NMR (CDCl3, 500 MHz): δ = 3.64 (d, 3 H, J = 10.7 Hz), 3.83 (3 H, J = 10.7 Hz), 4.99 (d, 1 H, J = 25.0 Hz), 5.12 (br s, 1 H, NH), 6.62-6.73 (m, 3 H), 7.11-7.13 (m, 2 H), 7.88-8.40 (m, 4 H). 13C NMR (CDCl3, 125 MHz): δ = 54.1 (d, ² J PC = 6.8 Hz), 54.6 (d, ² J PC = 5.9 Hz), 54.8 (d, ¹ J PC = 155.0 Hz), 114.2 (d, J PC = 11.2 Hz), 119.3 (d, J PC = 11.4 Hz), 123.2, 129.7 (d, J PC = 4.5 Hz), 130.0 (d, J PC = 11.2 Hz), 134.3 (d, J PC = 3.9 Hz), 139.9, 145.9 (d, J PC = 13.8 Hz), 148.9 (d, J PC = 2.5 Hz). 4n: IR (KBr): 3300 cm-1 (NH). 1H NMR (CDCl3, 500 MHz): δ = 0.77 (t, 3 H, J = 6.9 Hz), 1.37 (t, 3 H, J = 7.0 Hz), 3.26 (m, 1 H), 3.79 (m, 1 H), 4.26 (m, 2 H), 5.01 (br s, 1 H, NH), 5.75 (d, 1 H, J = 24.1 Hz), 6.63-6.70 (m, 3 H), 7.06-7.09 (m, 2 H), 7.45-7.93 (m, 6 H), 8.33-8.35 (m, 1 H). 13C NMR (CDCl3, 125 MHz): δ = 16.3 (d, ³ J PC = 2.3 Hz) 17.0 (d, ³ J PC = 5.8 Hz), 51.8 (d, ¹ J PC = 151 Hz), 63.6 (d, ² J PC = 6.5 Hz), 63.9 (d, ² J PC = 5.8 Hz), 113.9, 114.1, 118.6, 123.4 (d, J PC = 6.6 Hz), 126.2, 126.2, 126.7, 128.8, 129.0, 129.4, 129.6 (d, J PC = 10.6 Hz), 132.0 (d, J PC = 5.0) 134.3, 146.6 (d, J PC = 14.5 Hz). 4u: IR (KBr): 3320 cm-1 (NH). 1H NMR (CDCl3, 500 MHz): δ = 1.13-2.13 (m, 10 H), 3.45(br s, NH), 3.54 (d, 6 H, J = 10.2 Hz), 6.66-7.05 (m, 5 H). 13C NMR (CDCl3, 125 MHz): δ = 20.2 (d, J PC = 10.5 Hz), 25.6, 30.5, 53.3 (d, J PC = 7.7 Hz), 58.1 (d, J PC = 159.0 Hz), 118.6 (d, J PC = 10.5 Hz), 119.6 (d, J PC = 13.2 Hz), 129.0 (d, J PC = 6.7 Hz), 146.1.