The Alkylation of Aminophosphanes: A New Synthesis of Iminophosphoranes

Abstract

Iminophosphoranes are prepared by P-alkylation of easily available N,P,P-trisubstituted aminophosphanes with reactive alkyl halides and further deprotonation.

alkyl halides - alkylation - phosphorus - ylides - iminophosphoranes

References

1a Gusar NI. Russ. Chem. Rev. (Engl. Transl.)  1991,  60:  146 

1b Barluenga J. Palacios F. Org. Prep. Proced. Int.  1991,  23:  1 

1c Eguchi S. Matsushita Y. Yamashita K. Org. Prep. Proced. Int.  1992,  24:  209 

1d Johnson AW. Kaska WC. Ostoja-Starzewski KA. Dixon DA. In Ylides and Imines of Phosphorus   Johnson AW. Wiley; New York: 1993.  p.403 

1e Molina P. Vilaplana MJ. Synthesis  1994,  1197 

2a Staudinger H. Meyer J. Helv. Chim. Acta  1919,  2:  635 

2b Gololobov YG. Zhmurova IN. Kasukhin LF. Tetrahedron  1981,  37:  437 

2c Gololobov Y. Kasukhin LF. Tetrahedron  1992,  48:  1353 

3 Horner L. Oediger H. Liebigs Ann. Chem.  1959,  627:  142 

4a Alajarín M. López-Leonardo C. Llamas-Lorente P. Bautista D. Synthesis  2000,  2085 

4b Alajarín M. López-Leonardo C. Llamas-Lorente P. Tetrahedron Lett.  2001,  42:  605 

4c Alajarín M. López-Leonardo C. Llamas-Lorente P. Tetrahedron Lett.  2001,  42:  1041 

4d Alajarín M. López-Leonardo C. Llamas-Lorente P. Bautista D. Jones PG. Dalton Trans.  2003,  426 

5 Sisler HH. Smith NL. J. Org. Chem.  1961,  26:  4733 

6 The more polarizable, heavier element P should show greater nucleophilicity, see: Quin LD. A Guide to Organophosphorus Chemistry   John Wiley and Sons; New York: 2000.  p.129 

7 Kato S. Goto M. Hattori R. Nishiwaki K. Mizuta M. Ishida M. Chem. Ber.  1985,  118:  1668 

8

Typical Procedure for the Synthesis of Bromides 1: To a solution of 4-tolylaminodiphenylphosphane (0.3 g, 1.03 mmol) in dry Et₂O (15 mL) was added benzyl bromide (0.25 g, 1.5 mmol). The mixture was stirred for 6 h under N₂ atmosphere. The appearance of a white precipitate of 1j was observed, which was filtered, washed with Et₂O (5 mL) and dried under reduced pressure. An analytically pure sample was obtained by recrystallization from CH₂Cl₂-Et₂O (white prisms). Yield (0.37 g, 77%); mp 176-178 ºC. IR (nujol): 2758, 1515, 1437, 1386, 1116, 750, 698 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.15 (s, 3 H, CH₃), 4.72 (d, 2 H, ² J _HP = 16.2 Hz, CH₂P), 6.84 (d, 2 H, ³ J _HH = 8.2 Hz, H_arom), 6.91-6.93 (m, 4 H, H_arom), 7.11 (t, 2 H, ² J _HH = 7.4 Hz, H_arom), 7.22 (m, 1 H, H_arom), 7.51-7.56 (m, 4 H, H_arom), 7.63-7.74 (m, 6 H, H_arom), 10.07 (d, 1 H, ² J _HH = 8.6 Hz, NH). ¹³C {¹H} NMR (75 MHz, CDCl₃): δ = 20.60 (CH₃), 34.45 (d, ¹ J _CP = 61.6 Hz, CH₂P), 118.87 (d, ¹ J _CP = 95.7 Hz, q, C _i ), 120.17 (d, ³ J _CP = 7.1 Hz, C_arom), 127.00 (d, ² J _CP = 7.4 Hz, q, C_arom), 128.37 (d, ⁵ J _CP = 4.2 Hz, C_arom), 128.78 (d, ⁴ J _CP = 3.5 Hz, C_arom), 129.71 (d, ³ J _CP = 12.9 Hz, C _m ), 129.73 (C_arom), 131.01 (d, ³ J _CP = 5.7 Hz, C_arom), 132.96 (q, C_arom), 133.57 (d, ² J _CP = 10.1 Hz, C _o ), 134.93 (d, ⁴ J _CP = 3.0 Hz, C _p ), 135.63 (d, ² J _CP = 3.8 Hz, q, C_arom). ³¹P {¹H} NMR (121 MHz, CDCl₃): δ = 35.36. MS (EI): m/z (rel. intensity) = 383 (4) [M⁺ + 1 - Br], 382 (29) [M⁺ - Br], 381 (100) [M⁺ - HBr], 183 (46). Anal. Calcd for C₂₆H₂₅BrNP: C, 67.54; H, 5.45; N, 3.03. Found: C, 67.62; H, 5.62; N, 3.21.

9

Typical Procedure for the Synthesis of Iminophos-phoranes 2: To a suspension of 1j (0.3 g, 0.65 mmol) in dry C₆H₆ (20 mL) was added Et₃N (0.08 g, 0.8 mmol). The mixture was stirred for 1 h under N₂ atmosphere and the precipitate of Et₃N⟨HBr was filtered. The solvent from the filtrate was removed under vacuum and the residue was triturated with dry Et₂O (10 mL). White crystalline 2j was isolated by filtration and dried under reduced pressure. An analytically pure sample was obtained by recrystallization from CH₂Cl₂-Et₂O (white prisms). Yield (0.24 g, 97%); mp 138-140 ºC. IR(nujol): 1506, 1438, 1329, 1109, 1026, 910, 822 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.20 (s, 3 H, CH₃), 3.91 (d, 2 H, ² J _HP = 14.2 Hz, CH₂P), 6.67 (d, 2 H, ³ J _HH = 8.1 Hz, H_arom), 6.84-6.86 (m, 4 H, H_arom), 7.08-7.15 (m, 3 H, H_arom), 7.37-7.44 (m, 4H, H_arom), 7.49-7.53 (m, 2H, H_arom), 7.62-7.67 (m, 4H, H_arom). ¹³C {¹H} NMR (CDCl₃, 100 MHz): δ 20.61 (CH₃), 35.71 (d, ¹ J _CP = 64.7 Hz, CH₂P), 122.81 (d, ³ J _CP = 18.0 Hz, C_arom), 126.84 (d, ⁵ J _CP = 2.1 Hz, C_arom), 128.13 (d, ⁴ J _CP = 2.6 Hz, C_arom), 128.40 (q, C_arom), 128.66 (d, ³ J _CP = 11.5 Hz, C _m ), 129.43 (C_arom), 130.57 (d, ³ J _CP = 5.0 Hz, C_arom), 130.67 (d, ¹ J _CP = 90.7 Hz, q, C _i ), 131.91 (br s, C _p ), 132.26 (d, ² J _CP = 8.9 Hz, C _o ), 134.88 (d, ² J _CP = 10.27.4 Hz, q, C_arom), 148.63 (d, ² J _CP = 2.9 Hz, q, C_arom). ³¹P {¹H} NMR (161 MHz, CDCl₃): δ = 7.08. MS (EI): m/z (rel. intensity) = 382 (24) [M⁺ + 1], 381 (79) [M⁺], 380 (25) [M⁺ - 1), 290 (100). Anal. Calcd for C₂₆H₂₄NP: C, 81.87; H, 6.34; N, 3.67. Found: C, 81.75; H, 6.50; N, 3.75.

10 In solution, iminophosphoranes 2f-h exist in the enol tautomeric form, forming intramolecular hydrogen-bonded six membered ring (Scheme 5). This is clearly apparent from their NMR spectra, where the characteristic signals of the P-CH=C(Ar)-OH fragment are observed, and also by the absence of the carbonyl absorption in their IR spectra. The enol OH structure is believed to be favoured over the C-H form as result of the favourable intramolecular N˙˙˙H-O hydrogen bond, see: Steiner T. Angew. Chem. Int. Ed.  2002,  41:  48 

11 Baechler RD. Blohm M. Rocco K. Tetrahedron Lett.  1988,  29:  5353 

12

Compound 6: Colorless prisms (from CH₂Cl₂-Et₂O), mp 181-183 ºC. IR (nujol): 3390, 1515, 1439, 1182, 1121, 778, 721 cm^{- 1}. ¹H NMR (400 MHz, CDCl₃): δ = 2.24 (s, 3 H, CH₃), 3.76 (d, 2 H, ² J _HP = 13.2 Hz, CH₂P), 4.18 (s, 2 H, CH₂N), 6.60 (d, 2 H, ³ J _HH = 8.5 Hz, H_arom), 6.80 (dt, 1 H, ⁴ J _HH = 1.7 Hz, ³ J _HH = 7.7 Hz, H_arom), 6.98 (d, 2 H, ³ J _HH = 8.5 Hz, H_arom), 7.05 (dd, 1 H, ⁴ J _HH = 1.1 Hz, ³ J _HH = 7.5 Hz, H_arom), 7.16 (dt, 1 H, ⁴ J _HH = 1.7 Hz, ³ J _HH = 7.5 Hz, H_arom), 7.32 (m, 1 H, H_arom), 7.38-7.57 (m, 6 H, H_arom), 7.62-7.74 (m, 4 H, H_arom), NH proton obscured. ¹³C {¹H} NMR (100 MHz, CDCl₃): δ = 20.49 (CH₃), 34.70 (d, ¹ J _CP = 65.8 Hz, CH₂P), 47.47 (CH₂N), 113.16 (C_arom), 126.49 (q, C_arom), 127.41 (d, J _CP = 6.6 Hz, C_arom), 127.42 (C_arom), 128.65 (d, ³ J _CP = 11.7 Hz, C _m ), 129.71 (C_arom), 130.15 (d, ³ J _CP = 8.4 Hz, q, C_arom), 130.34 (d, J _CP = 2.6 Hz, C_arom), 131.06 (d, J _CP = 4.5 Hz, C_arom), 131.37 (d, ² J _CP = 9.2 Hz, C _o ), 132.02 (d, ⁴ J _CP = 2.8 Hz, C _p ), 132.24 (d, ¹ J _CP = 97.3 Hz, q, C _i ), 138.46 (d, ² J _CP = 5.2 Hz, q, C_arom), 146.22 (q, C_arom). ³¹P {¹H} NMR (161 MHz, CDCl₃): δ = 30.74. Anal. Calcd for C₂₇H₂₆NOP: C, 78.81; H, 6.37; N, 3.40. Found: C, 78.62; H, 6.32; N, 3.23.

13 Hudson HR. In The Chemistry of Functional Groups. The Chemistry of Organophosphorus Compounds   Vol. 1:  Hartley FR. Patai S. John Wiley and Sons; Chichester: 1990.  p.387 

14 Lindner E. Khanfar M. Steimann M. Eur. J. Inorg. Chem.  2001,  2411 

15

Compound 8: Colorless prisms (from CHCl₃-Et₂O), mp 227-229 ºC. IR (nujol): 1437, 1182, 1099, 1029, 751, 693 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.49 (s, 3 H, CH₃), 3.95 (d, 2 H, ² J _HP = 13.8 Hz, CH₂P), 7.37-7.42 (m, 4 H, H_arom), 7.44-7.48 (m, 2 H, H_arom), 7.50-7.80 (m, 4 H, H_arom). ¹³C {¹H} NMR (100 MHz, CDCl₃): δ = 19.89 (CH₃), 38.30 (d, ¹ J _CP = 50.4 Hz, CH₂P), 128.52 (d, ³ J _CP = 12.4 Hz, C _m ), 129.18 (m, q, C_arom), 131.45 (C _p ), 131.68 (d, ² J _CP = 9.9 Hz, C _o ), 133.34 (d, ¹ J _CP = 76.6 Hz, q, C _i ), 137.17 (m, q, C_arom). ³¹P {¹H} NMR (161 MHz, CDCl₃): δ = 38.84. MS (FAB⁺): m/z (rel. intensity) = 812 (45) [M⁺ + 1].

16 Wetzel TG. Dehnen S. Roesky PW. Angew. Chem. Int. Ed.  1999,  38:  1086