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

doi:10.1055/s-2002-32957

LETTER

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;

Abstract

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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.

Key words

amino phosphonate - imine - trialkylphosphite - lithium perchlorate

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References

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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.