Reaction of Non-Racemic (1-Phenyl)ethylamines with Chloromethyl­isothiocyanatothiophosphonates: Synthesis of Optically Active 1,3,4-Thiazaphospholes

Abstract

Both enantiomers of the major diastereomer of 2-(1-­phenyl)ethylamino-4-thioxo-4-phenoxy-1,3,4-thiazaphosphol-2-ine were obtained in optically pure form by the reaction of O-­phenyl(chloromethyl)isothiophosphonate with (R)-(+)- and (S)-(-)-(1-phenyl)ethylamine.

organophosphorus compounds - chloromethylisothio­cyanatothiophosphonates - thiazaphospholes - enantiomers

References and Notes

1 Kolodiazhnyi OI. Tetrahedron: Asymmetry  1998,  9:  1279 

2 Kukhar VP. Hudson HR. Aminophosphonic and Aminophosphinic Acids: Chemistry and Biological Activity   John Wiley & Sons Inc.; New York: 2000.  p.634 

3 Kafarski P. Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  63:  193 

4 Kamalov RM. Khailova NA. Gazikasheva AA. Chertanova LF. Pudovik MA. Pudovik AN. Dokl. Akad. Nauk. SSSR  1991,  6:  1406 

5 Khailova NA. Krepysheva NE. Saakyan GM. Bagautdinova RKh. Shaimardanova AA. Azancheev NM. Litvinov IA. Gubaidullin AT. Zverev VV. Pudovik MA. Pudovik AN. Zh. Obshch. Khim.  2002,  72:  1145 

6

( R _C , S _P )-2-(1-Phenyl)ethylamino-4-thioxo-4-phenoxy-1,3,4-thiazaphosphole ( 4b)
To 1 (2.0 g, 7.53 mmol, 1 equiv) in anhyd benzene (25 mL) at 0 °C was added a mixture of Et₃N (0.38 g, 3.76 mmol) and 3 (0.46 g, 3.76 mmol, 0.5 equiv). After standing at r.t. for 16 h, Et₃N·HCl was removed by filtration, the solvent was removed, and the crystalline product was recrystallized from benzene. Yield: 19.0%; mp 161.5-163 °C; [α]_D ²⁰ +290.1 (c 2.44, CH₃CN). IR: 685, 1210, 1570, 1590, 3275 cm^-1. ¹H NMR [400 MHz, (CD₃)₂CO]: δ = 1.54 (d, J = 7.0 Hz, 3 H), 3.49 (dd, J = 13.3, 3.6 Hz, 1 H), 3.81 (dd, J = 13.3, 13.3 Hz, 1 H), 5.23 (dq, J = 7.0, 7.0 Hz, 1 H), 6.79-7.40 (m, 10 H), 8.28 (s, 1 H). ¹³C NMR [100.62 MHz, (CD₃)₂CO]: δ = 22.37 (CH₃), 35.18 (d, CH₂, J _PC = 56.88 Hz, J _HH = 144.27 Hz), 55.35 (CH), 167.61 (N=C), 151.74 (C _i OP, d, J _PC = 9.71 Hz), 144.24 (C _i ), 122.34 (C _o , J _CH = 162.3 Hz), 125.23 (C _o , J _CH = 159.53 Hz), 129.23 (C _m , J _CH = 159.53 Hz), 129.89 (C _m , J _CH = 160.91 Hz), 126.87 (C _p , J _CH = 160.91 Hz), 127.96 (C _p , J _CH = 159.53 Hz). ³¹P NMR [(CD₃)₂CO, 162.98 MHz]: δ = 120.67. Anal. Calcd for C₁₆H₁₇N₂OPS_2: C, 55.14; H, 4.93; N, 8.04; P, 8.82; S, 18.41. Found: C, 55.47; H, 4.85; N, 8.02; P, 9.32; S, 18.23.
To 1 (2.0 g, 7.53 mmol, 1 equiv) in anhyd benzene (25 mL) at 0 °C was added a mixture of Et₃N (0.53 g, 5.26 mmol, 0.7 equiv) and 3 (0.64 g, 5.26 mmol). Product 4b was isolated by the same procedure described above. Yield: 30.5%; mp 161.5-162 °C; [α]_D ²⁰ +289.3 (c 2.41, CH₃CN). This product has similar spectral data.
The spectral data for 4a (from the mixture of diastereomers). ¹H NMR [400 MHz, (CD₃)₂CO]: δ = 1.59 (d, J = 7.0 Hz, 3 H), 3.51 (dd, J = 13.3, 3.3 Hz, 1 H,), 3.89 (dd, J = 12.9, 2.9 Hz, 1 H), 5.35 (q, J = 7.0 Hz, 1 H), 7.12-7.43 (m, 10 H). ³¹C NMR [162.98 MHz, (CD₃)₂CO]: δ = 120.03.

7

( S _C, R _P )-2-(1-Phenyl)ethylamino-4-thioxo-4-phenoxy-1,3,4-thiazaphosphole ( 4d) Yield: 21.0%; mp 160-163 °C; [α]_D ²⁰ -277.4 (c 1.71, CH₃CN). ¹H NMR [400 MHz, (CD₃)₂CO]: δ = 1.53 (d, J = 8.0 Hz, 3 H), 3.50 (dd, J = 13.2, 3.9 Hz, 1 H), 3.80 (dd, J = 13.1, 13.1 Hz, 1 H), 5.23 (dq, J = 6.0, 6.0 Hz, 1 H), 6.8-7.30 (m, 10 H), 8.30 (s, 1 H). ¹³C NMR [100.62 MHz, (CD₃)₂CO]: δ = 21.93 (CH₃), 34.34 (d, CH₂, J _PC = 56.16 Hz, J _HH = 146.17 Hz), 54.73 (CH), 167.07 (N=C), 151.03 (C _i OP, d, J _PC = 9.63 Hz), 143.84 (C _i ), 121.81 (C _o , J _CH = 162.22 Hz), 124.72 (C _o , J _CH = 159.01 Hz), 129.35 (C _m , J _CH = 159.01 Hz), 128.76 (C _m , J _CH = 160.62 Hz), 126.29 (C _p , J _CH = 154.2 Hz), 127.37 (C _p , J _CH = 159.01 Hz). ³¹P NMR [162.98 MHz, (CD₃)₂CO]: δ = 120.26.
The spectral data for 4c (from a mixture of diastereomers). ¹H NMR [400 MHz, (CD₃)₂CO]: δ = 1.51 (d, J = 7.0 Hz, 3 H), 3.52 (dd, J = 13.3, 3.6 Hz, 1 H), 3.83 (dd, J = 13.3, 13.3 Hz, 1 H), 5.30 (q, J = 7.0 Hz, 1 H,), 7.14-7.39 (m, 10 H). ³¹P NMR [162.98 MHz, (CD₃)₂CO]: δ = 120.17.

8a

Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 264300 and 264301. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax:[phone] or e-mail: [e-mail]]

8b

Data set was collected on an Enraf Nonius CAD4 diffractometer.

8c Programs used: Data collection EXPRESS   Nonius B.V.; Delft: 1994. 

8d Data reduction and structure solution: Fair K. MolEN   Enraf-Nonius B.V.; Delft: 1990. 

8e Structure refinement: Sheldrick GM. SHELXL-97   University of Göttingen; Germany: 1997. 

8f Graphics: Keller E. SCHAKAL-97   University of Freiberg; Germany: 1997. 

8g

Formula C₁₆H₁₇N₂OPS₂, M = 348.41, colorless crystal 0.45 × 0.25 × 0.10 mm, a = 5.682 (4), b = 15.000(10), c = 10.490 (9) Å, β = 105.12 (6)°, V = 863.1 (11) ų, ρ_calc = 1.341 gcm^-3, µ = 3.68 cm^-1, empirical absorption correction (0.288 < T < 0.709), Z = 2, monoclinic, space group P2₁ (No. 4), λ = 1.54184 Å, T = 293 K, ω scans, 2402 reflections collected (+h, ±k, ±l), [(sinθ)/λ] = 0.66 Å^-1, 1770 independent observed reflections [I - 2 σ(I)] (Rint = 0.041), 200 refined parameters, R = 0.055, wR2 = 0.144, max. residual electron density 0.28 (-0.25) eÅ^-3, hydrogen atoms at nitrogen atoms obtained from difference Fourier calculations, others calculated and refined as riding atoms.