Download PDF
Synlett 2003(15): 2321-2324  
DOI: 10.1055/s-2003-42118
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Catalytic Three-Component Synthesis (Kabachnick-Fields Reaction) of α-Aminophosphonates from Ketones

Elena D. Matveeva*, Tatyana A. Podrugina, Elena V. Tishkovskaya, Larisa G. Tomilova, Nikolay S. Zefirov*
Department of Chemistry, Moscow Lomonosov University, Moscow, Russia
Fax: +7(95)9390290; e-Mail: edmatveeva@mail.ru; e-Mail: zefirov@org.chem.msu.ru;
Further Information

Publication History

Received 11 July 2003
Publication Date:
07 November 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

A novel and highly convenient catalytic variant of the synthesis of α-aminophosphonates on basis of the Kabachnik-Fields reaction [three-component reaction of ketones, diethylphosphite and either benzylamine (series a) of ammonium carbonate (series b)] in the presence of tetra-tert-butylphthalocyanines has been developed. This method affords α-aminophosphonates in acceptable yields for various ketones, including cyclic, sterically hindered and cage ketones. The unsubstituted α-aminophosphonic acids were also obtained from the corresponding esters of series b.

Key words

α-aminophosphonates - catalysis - tetra-tert-butyl­phthalocyanines - ketones - α-aminophosphonic acids

25

General Procedure: To the solution of ketone (2 mmol) in solvent (3 mL, see Table [1] ), the benzylamine (2 mmol) or NH4(CO3)2 (6 mmol), anhyd MgSO4 (2 mmol) and Pht-1 [22] (10 mol%; 0.2 mmol) as a catalyst were added. The reaction mixture was heated for 3-4 h. Then diethylphosphite (2.4 mmol) was added. The reaction mixture was stirred for 12-24 h (see Table [1] ). The desiccant was then filtered and washed with 2 mL of CH2Cl2. The solvent was evaporated, and the residue was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH = 20:1). In the case of steric hindered and cage ketones (adamantanone-2, camphor and norbornanone) 50% amine excess is required.

26

All obtained compounds gave satisfactory elemental analyses with the range of C ±0.3%, H ±0.2%, N ±0.3%.

27

IR spectra registration was carried out in condensed phase and in the solution in CCl4. There are stretches absorptions at 1200 cm-1 (P=O), 3200-3400 cm-1 (N-H and NH2) and 1180 cm-1 (C-O) in the IR spectra of given compounds. IR spectra of α-benzylaminophosphonates solutions were measured under the dilution forty times over. At that intensity and frequency the absorption bands of phosphonic and NH-associated groups did not change. This fact is evidence of the presence of intramolecular hydrogen bonds.

28

Selected NMR data are presented below. Compound 1a. 1H NMR (400 MHz, CDCl3): δ = 0.88 (d, 3 H, CH3-cycl.), 1.34, 1.36 (2 t, 6 H, 2CH3), 1.53, 1.66, 1.87 (3 m, 9 H, cycl., NH), 3.92 (d, 3 J PH = 3.2 Hz, 2 H, CH2-Bz), 4.16 (br m, 4 H, OCH2), 7.31, 7.38 (2 m, 5 H, arom.) ppm. 13C NMR (400 MHz, CDCl3): δ = 16.32 (d, 3 JCP = 4.6 Hz, CH3), 19.68 (d, J = 12.2 Hz, CH3, cycl.), 22.15, 25.38, 28.65, 34.09, 37.61 (cycl.), 46.84 (CH2-Bz), 56.30 (d, 1 JPC = 141.9 Hz, C-1), 61.83, 61.34 (2 JPC = 6.1 Hz, OCH2), 126.39, 127.78, 127.87, 141.09 (C arom.) ppm. 31P NMR (400 MHz, CDCl3): δ = 28.52 ppm. IR: 1240 (P=O), 3340, 3470 (NH) cm-1.
Compound 10a. 1H NMR (400 MHz, CDCl3): δ = 1.12, 1.27 (2 t, 6 H, 2CH3), 1.34, 1.64, 2.10, 2.24 (4 m, 14 H, cycl.), 2.75 (br s, 1 H, NH), 3.55 (A part AB syst, J AB = 13.2 Hz, 1 H, CH2Bz), 3.83 (B part AB syst, JAB = 13.2 Hz, 1 H, CH2Bz), 3.80, 3.94, 4.10 (3 m, 4 H, OCH2), 7.27, 7.37 (2 m, 5 H, Ar) ppm. 13C NMR: δ = 16.36, 16.58 (2 d, 3 JCP = 6.3 Hz, CH3), 24.66, 25.29, 31.31, 34.13, 35.82, 44.18 (cycl.), 51.19 (d, J = 12.6 Hz, CH2-Bz), 60.12 (d, 1 JPC = 154.1 Hz, C-1, cycl.), 62.98, 63.15, (2 JPC = 7.8 Hz, OCH2), 127.29, 128.10, 128.52, 128.87 (C Ar). 31P NMR: δ = 22.5 ppm. IR: 1235 (P=O), 3260, 3360 (NH) cm-1. Anal. Calcd for C21H32NPO3(377): C, 66.84; H, 8.49; N, 3.71; P, 8.22. Found: C, 67.87; H, 7.50; N, 3.57.
Compound 10b. 1H NMR (CDCl3): δ = 1.36 (t, 6 H, 2CH3), 1.52, 1.74, 1.85, 2.13, (3 m, 10 H, cycl.), 2.35, 2.42 (2 m, 4 H cycl.), 3.01 (br s, 2 H, NH2), 4.21 (m, 4 H, OCH2), 7.27, 7.37 (2 m, 5 H, Ar) ppm. 13C NMR: δ = 16.08 (CH3), 26.13, 26.62, 31.66, 31.77, 33.27, 33.41, 38.77, 46.88 (cycl.), 62.19 (d, 2 JPC = 7.8 Hz, OCH2) ppm. 31P NMR: δ = 25.39 ppm. IR: 1245 (P=O), 3280 (NH2) cm-1.
Compound 12a. 1H NMR (CDCl3): δ = 1.05, 1.15 (2 m, 2 H, cycl.), 1.34, 1.35 (2 t, 6 H, 2CH3), 1.51, 1.88, 2.12, 2.26, 2.60 (5 m, 10 H, cycl.), 3.69 (A part AB syst., JAB = 13.4 Hz, 1 H, CH2Bz), 3.85 (B part AB syst, J AB = 13.4 Hz, 1 H, CH2Bz), 3.99-4.23 (m, 4 H, OCH2), 7.21, 7.31, 7.37 (3 m, 5 H, Ar) ppm. 31P NMR: δ = 30.53, 31.44 (2 s, 2:1) ppm.

29

These signals are at 1.30-1.36 ppm (t, CH3) and at 4.10-4.20 ppm (complicated multiplet OCH2 2 J PH = 3.1 Hz).

30

In 1H NMR spectra, the protons of CH3 groups were observed at δ = 1.15 and 1.30 ppm (2 t, 1:1). The diastereo-topic protons of two diastereotopic OCH2 groups appear as several multiplets at 3.80-4.50 ppm (2 J PH = 3.1 Hz): either four multiplets in ratio 1:1:1:1 or the superposition of three multiplets in ratio 1:2:1. In 1H NMR spectra of α-benzyl-aminophosphonates (series a) the signals of diastereotopic benzyl protons resonate at 3.50-3.70 ppm as two doublets (JAB = 12.8 Hz).

31

There is the corresponding duplication of signals of the diastereotopic ethoxy group in 13C NMR spectra. In fact, CH3 groups resonate as two doublets at δ = 16.00 ppm (3 J PC = 6.3-6.5 Hz) and the OCH2 group as two doublets at 62.00-63.00 ppm (2 J PC = 8.6 Hz). These values are in agreement with available literature data. [24] The quaternary carbon atom resonates at δ = 50.00-60.00 ppm (1 J PC = 140-150 Hz). [27]