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Synlett 2018; 29(07): 933-937
DOI: 10.1055/s-0036-1591919
DOI: 10.1055/s-0036-1591919
letter
Synthesis of Symmetrical N-Aryl-C-phosphonoacetamidines
This work was financially supported by the Russian Foundation for Basic Research (Grant no. 16-03-00474).
Further Information
Publication History
Received: 05 December 2017
Accepted after revision: 04 January 2018
Publication Date:
06 February 2018 (online)
Abstract
An efficient synthesis of a series of novel symmetrical N-aryl-C-phosphonoacetamidines through reaction of diisopropyl (chloroethynyl)phosphonate with primary aryl amines was developed. This procedure tolerates a wide range of functional groups and has a good atom economy. The (E)-isomer was the major product that crystallized preferentially over the (Z)-isomer.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591919.
- Supporting Information
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- 26 N-Aryl-C-phosphonoacetamidines 3a–s; General Procedure The appropriate aniline 2a–s (2 mmol) was added to a mixture of diisopropyl (chloroethynyl)phosphonate (1; 1 mmol) and K2CO3 (1 mmol) in anhyd acetonitrile (10 mL) at r.t., and the mixture was stirred vigorously under reflux for 5–25 h. When the reaction was complete, the mixture was filtered and concentrated, and the residue was crystallized from hexane. Diisopropyl {(2E)-2-[(4-Fluorophenyl)amino]-2-[(4-fluorophenyl)imino]ethyl}phosphonate (3e) White needle crystals; yield: 332 mg (81%); mp 104–106 °C. IR (KBr): 995.27 (P–O–C), 1226.73 (P=O), 1500.62 (C=N) cm–1. 1H NMR (400.13 MHz, DMSO-d 6): δ = 1.16 (d, 3 J HH = 6.1 Hz, 6 H, CH3), 1.21 (d, 3 J HH = 6.2 Hz, 6 H, CH3), 2.92 (d, 2 J HP = 21.8 Hz, 2 H, CH2P), 4.53 (m, 3 J HH = 6.1 Hz, 3 J HP = 12.4 Hz, 1 H, CHOP), 4.54 (m, 3 J HH = 6.1 Hz, 3 J HP = 14.0 Hz, 1 H, CHOP), 6.82 [m, 3 J HH = 8.8 Hz, 1 H, o-CH, Ar(NH)], 6.83 [m, 3 J HH = 8.8 Hz, 1 H, o-CH, Ar(NH)], 7.09 (m, 3 J HH = 9.1 Hz, 4 H, m-CH, Ar), 7.73 [m, 3 J HH = 9.2 Hz, 1 H, o-CH, Ar(N=)], 7.75 [m, 3 J HH = 9.2 Hz, 1 H, o-CH, Ar(N=)], 8.66 (s, 1 H, NH). 13C NMR (100.61 MHz, DMSO-d 6): δ = 23.97 (d, 3 J CP = 4.4 Hz, CH3), 24.11 (d, 3 J CP = 4.4 Hz, CH3), 30.25 (d, 1 J CP = 133.5 Hz, CH2P), 70.98 [d, 2 J CP = 6.6 Hz, (OCH)2P], 115.38 [d, 2 J CF = 21.3 Hz, m-CH, Ar(NH)], 115.59 [d, 2 J CF = 22.0 Hz, m-CH, Ar(N=)], 121.02 [d, 3 J CF = 7.3 Hz, o-CH, Ar(NH)], 123.50 [d, 3 J CF = 8.0 Hz, o-CH, Ar(N=)], 137.57 (d, 4 J CF = 1.5 Hz, C-ipso-N=), 146.67 (d, 4 J CF = 1.5 Hz, C-ipso-NH), 148.09 (d, CH2 C, 2 J CP = 7.3 Hz), 157.62 [d, 1 J CF = 239.1 Hz, CF, Ar(NH)], 158.40 [d, 1 J CF = 237.6 Hz, CF, Ar(N=)]. 31P NMR (161.98 MHz, DMSO-d 6): δ = 20.63. 19F NMR (376.50 MHz, DMSO-d 6): δ = –122.72 [F, Ar(NH)], –121.19 [F, Ar(N=)]. ESI-HRMS: m/z [M + H]+ calcd for C20H26F2N2O3P: 411.1660; found: 411.1644.
- 27 CCDC 1505945 and CCDC 1518068 contain the supplementary crystallographic data for compounds 3k and 3l, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.