Synthesis of Tetrazole-Containing C-Phosphonoacetamidines

Abstract

Addition of 5-substituted tetrazoles to dialkyl 2-(N-tert-butyl- or N-adamantyl)iminovinylphosphonates proceeds regioselectively to yield novel tetrazole-containing phosphonoacetamidines – 2-[(N-tert-butyl- or N-adamantyl)imino-2-(tetrazolyl)ethyl]phosphonic acid dialkyl esters – with good yields. The reactions occur via nucleophilic attack of the tetrazole N-1 atom at the C=C bond.

Key words

NH-tetrazoles - C-phosphonoketenimines - C-phosphonoamidines - imino phosphonates - phosphorylated acetamidines

• References and Notes

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• 38 Typical Experimental Procedure for the Synthesis of Compounds 3a–l A mixture of dimethyl 2-N-tert-butyliminoethenephosphonate (1a, 25 mmol) or diethyl 2-(N-adamant-1-yl)iminoethenephosphonate (1b) and the corresponding NH-tetrazole 2a–f (25 mmol) in anhydrous CCl₄ (10 mL) was stirred vigorously under reflux for 15 h. After the reaction was completed, the solvent was removed. The residue was chromatographed on silica gel eluting with a mixture of EtOAc–hexane (1:3). (2-tert-Butylimino-2-tetrazol-1-ylethyl)phosphonic Acid Dimethyl Ester (3a) Yield 77%, pale yellow oil. ¹H NMR (400.13 MHz, CDCl₃): δ = 1.60 (s, 9 H, CH₃), 2.64 (d, ² J _PH = 24.1 Hz, 2 H, PCH₂), 3.67 (d, ³ J _HP = 10.9 Hz, 6 H, OCH₃), 8.17 (s, 1 H, CH, tetrazole). ¹³C NMR (100.61 MHz, CDCl₃): δ = 28.36 (s, CH₃, t-Bu), 35.04 (d, ¹ J _PC = 137.3 Hz, PCH₂), 51.59 (s, C, t-Bu), 53.11 (d, ² J _CP = 6.7 Hz, OCH₃), 140.16 (s, C, ring), 163.16 (d, ³ J _CP = 4.0 Hz, C=N). ³¹P NMR (161.98 MHz, CDCl₃): δ = 25.84. ESI-HRMS: m/z calcd for C₉H₁₉N₅O₃P: 276.1220; found: 276.1231 [M + H]⁺. [2-(Adamantan-1-ylimino)-2-(5-methyltetrazol-1-yl)ethyl]-phosphonic Acid Diethyl Ester (3h) Yield 82%, pale yellow oil. ¹H NMR (400.13 MHz, CDCl₃): δ =.17 (t, ³ J _HH = 7.4 Hz, 6 H, CH₃), 1.63 (br, 6 H, CH₂, adamant.), 1.78 (br, 6 H, CH₂, adamant.), 1.95 (m, 3 H, CH, adamant.), 2.28 (s, CH₃, tetrazole), 2.73 (d, ² J _PH = 20.6 Hz, 2 H, PCH₂), 4.12 (q, ³ J _HP = 7.3 Hz, 4 H, OCH₂). ¹³C NMR (100.61 MHz, CDCl₃): δ = 8.54 (s, CH₃, tetrazole), 16.06 (s, CH₃), 29.12 (CH, adamant.), 35.95 (d, ¹ J _PC = 131.8 Hz, PCH₂), 36.04 (s, γ-CH₂, adamant.), 40.94 (α-CH₂, adamant.), 52.26 (C–N, adamant.), 62.66 (d, CH₂OP, ² J _CP = 6.0 Hz), 152.41 (s, C, tetrazole), 163.32 (d, C=N, ² J _CP = 5.0 Hz). ³¹P NMR (161.98 MHz, CDCl₃): δ = 23.47. ESI-HRMS: m/z calcd for C₁₈H₃₀N₅O₃PNa: 418.4254; found: 418.4196 [M + Na]⁺.
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