NJC
Paper
in CH2Cl2 (15 mL), in CH2Cl2 (120 mL) under vigorous stirring. 3.98 (t, 8H, J = 7.2 Hz, ArOCH2CH2), 3.71 (q, 8H, J = 7.2 Hz,
The resulting mixture was stirred for 15 h and then all the CH2CH2NH), 3.13 (d, 4H, J = 12.4 Hz, ArCH2Ar), 2.36 (quintet,
volatiles were removed in vacuo. The residue was partitioned 8H, J = 7.2 Hz, OCH2CH2CH2N), 1.37 and 1.28 (d, 24H, J = 6.1 Hz,
between H2O (50 mL) and CH2Cl2 (50 mL) three times. The CH(CH3)2), 1.06 (s, 36H, t-Bu). 13C NMR: d = 162.6, 153.5, 153.4,
organic phase was dried over Na2SO4, the resulting solution was 148.3, 144.9, 144.7, 144.5, 133.7, 133.6, 125.4, 125.2, 123.0,
passed through a short plug of silica and the solvent was 73.0–72.3 (multiplet), 37.4, 34.0, 31.8, 31.4, 31.2, 30.7, 30.6,
removed in vacuo. The crude product was crystallized from 24.6–23.5 (multiplet). IR (nmax/cmÀ1): 2963, 1670, 1541, 1485,
CH2Cl2–hexane affording pure 11 (4.0 g, 92%). 1H NMR 1387, 1362, 1299, 1250, 1198, 1136, 1123, 1103, 989, 730, 669.
(CDCl3): d = 9.33 (s, 4H, PyzH), 8.65 (s, 4H, PyzH), 8.41 (t, 4H, HRMS-TOF (m/z): [M + 2H]2+ calcd 979.4864, found 979.5500.
J = 6.0 Hz, NH), 6.73 (s, 8H, ArH), 4.31 (d, 4H, J = 12.0 Hz,
ArCH2Ar), 3.92 (t, 8H, J = 6.0 Hz, ArOCH2CH2), 3.68 (q, 8H, J =
6.0 Hz, CH2CH2NH), 3.14 (d, 4H, J = 12.0 Hz, ArCH2Ar), 2.39
General procedure for the palladium catalyzed P–C coupling of bis-
and tetrakis(3-(6-chloropyrazine-2-carboxamido)propyl)calix-
[4]arenes with HPPh2. Formation of 13 and 16
(quintet, 8H, J = 6.0 Hz, OCH2CH2CH2N), 1.07 (s, 36H, t-Bu). 13
C
NMR: d = 162.4, 162.3, 153.4, 147.8, 147.7, 144.5, 142.5, 142.4,
133.8, 133.7, 133.6, 133.5, 125.4, 125.3, 125.2, 123.0, 73.1, 72.8,
34.1, 31.6. IR (nmax/cmÀ1): 2954, 2868, 1668, 1533, 1481, 1390,
1362, 1298, 1193, 1168, 1131, 1011, 912, 871, 733, 669. HRMS-
TOF (m/z): [M + H]+ calcd 1440.5684, found 1440.5892.
To a solution of bis- or tetrakis(3-(6-chloropyrazine-2-carboxa-
mido)propyl)calix[4]arene (1 mmol) and Pd(OAc)2 (1 mol% per
chloropyrazine moiety) in a CH3CN–toluene (1 : 1) mixture
(50 mL) HPPh2 (1 equiv. per chloropyrazine moiety) and DBU
(1 equiv. per chloropyrazine moiety) were subsequently added.
The resulting mixture was refluxed for 30 h and then the
solvent was removed in vacuo. The residue was partitioned
between H2O (50 mL) and EtOAc (50 mL). The organic phase
was dried over Na2SO4 and all the volatiles were removed
in vacuo. The resulting crude phosphines 13 and 16 were fully
characterized as their phosphine oxides 14 and 17, respectively.
General procedure for the palladium-catalyzed P–C coupling of
bis- and tetrakis(3-(6-chloropyrazine-2-carboxamido)propyl)-p-tert-
butylcalix[4]arenes with HPO(O-i-Pr)2. Formation of 12 and 15
To a solution of bis- or tetrakis(3-(6-chloropyrazine-2-carboxa-
mido)propyl)calix[4]arene (1 mmol) and Pd(dppf)Cl2 (1 mol%
per chloropyrazine moiety) in a CH3CN–toluene (1 : 1) mixture
(50 mL) HPO(O-i-Pr)2 (1.1 equiv. per chloropyrazine moiety) and
i-Pr2NEt (1.1 equiv. per chloropyrazine moiety) were sub-
sequently added. The resulting mixture was refluxed for 3 (12)
Bis(3-(6-(diphenylphosphino)pyrazine-2-carboxamido)propyl)-
p-tert-butylcalix[4]arene (13)
and 8 days (15), respectively, and then the solvent was removed 1H NMR: d = 9.17 (s, 2H, PyzH), 8.39 (s, 2H, PyzH), 8.08 (t, 2H,
in vacuo. The residue was partitioned between H2O (50 mL) and J = 6.0 Hz, NH), 7.80 (s, 2H, ArOH), 7.39–7.22 (m, 20H, Ph), 7.01
EtOAc (50 mL). The organic phase was dried over Na2SO4 and and 6.88 (s, 4H, ArH), 4.15 (d, 4H, J = 12.0 Hz, ArCH2Ar), 3.92
all the volatiles were removed in vacuo to give the crude 12 (t, 4H, J = 6.0 Hz, ArOCH2CH2), 3.80 (q, 4H, J = 6.0 Hz,
and 15. The crude products were purified by column chromato- CH2CH2NH), 3.21 (d, 4H, J = 12.0 Hz, ArCH2Ar), 2.22 (quintet,
graphy (neat EtOAc) affording pure compounds as brown oils 4H, J = 6.0 Hz, OCH2CH2CH2N), 1.23 and 1.04 (s, 18H, t-Bu).
which solidified upon standing.
Tetrakis(3-(6-(diphenylphosphino)pyrazine-2-
carboxamido)propyl)-p-tert-butylcalix[4]arene (16)
Bis(3-(6-(diisopropylphosphono)pyrazine-2-carboxamido)-
propyl)-p-tert-butylcalix[4]arene (12)
1H NMR: d = 9.13 (s, 4H, PyzH), 8.32 (s, 4H, PyzH), 8.05 (t, 4H,
Yield 1.0 g, 79%. 1H NMR: d = 9.47 (d, 2H, 3JHP = 3.6 Hz, PyzH), 9.16
J = 6.0 Hz, NH), 7.40–7.15 (m, 40H, Ph), 6.73 (s, 8H, ArH), 4.21
(s, 2H, PyzH), 8.24 (t, 2H, J = 5.9 Hz, NH), 7.52 (s, 2H, ArOH), 7.04 (s,
(d, 4H, J = 12.0 Hz, ArCH2Ar), 3.79 (t, 8H, J = 6.0 Hz,
4H, ArH), 6.84 (s, 4H, ArH), 4.92–4.79 (m, 4H, CH(CH3)2), 4.26 (d,
ArOCH2CH2), 3.48 (q, 8H, J = 6.0 Hz, CH2CH2NH), 3.05
4H, J = 12.9 Hz, ArCH2Ar), 4.09 (t, 4H, J = 6.6 Hz, ArOCH2CH2), 3.94
(d, 4H, J = 12.0 Hz, ArCH2Ar), 1.99 (quintet, 8H, J = 6.0 Hz,
(q, 4H, J = 6.6 Hz, CH2CH2NH), 3.34 (d, 4H, J = 12.9 Hz, ArCH2Ar),
OCH2CH2CH2N), 1.07 (s, 36H, t-Bu).
2.40 (quintet, 4H, J = 6.6 Hz, OCH2CH2CH2N), 1.38 and 1.28 (d,
12H, J = 6.2 Hz, CH(CH3)2), 1.27 and 0.98 (s, 18H, t-Bu). 13C NMR: d
Oxidation of phosphines 13 and 16. Formation of 14 and 17
= 162.9, 153.3, 147.3, 146.2, 133.4, 132.9, 127.9, 123.0, 122.0,
73.5–72.0 (multiplet), 34.2, 32.0, 31.9, 31.3, 31.2, 24.5–23.8 (multi- A solution of the crude phosphine and H2O2 (30% aqueous,
plet). IR (nmax/cmÀ1): 2962, 1671, 1541, 1485, 1387, 1376, 1362, 1.5 equiv., per PPh2 group) in acetone (25 mL) was stirred for
1298, 1249, 1197, 1124, 1102, 990, 910, 872, 731, 669. HRMS-TOF 12 h and then 1 M HCl (10 mL) was added. After stirring the
(m/z): [M + Na]+ calcd 1326.6806, found 1326.6843.
reaction mixture for 30 min all the volatiles were removed in
vacuo and the residue was partitioned between H2O (30 mL)
and CHCl3 (30 mL). The organic phase was dried over Na2SO4,
giving the corresponding phosphine oxides after evaporation of
Tetrakis(3-(6-(diisopropylphosphono)pyrazine-2-carboxamido)-
propyl)-p-tert-butylcalix[4]arene (15)
Yield 1.2 g, 61%. 1H NMR: d = 9.47 (d, 4H, 3JHP = 3.5 Hz, PyzH), the solvent as yellow oils. The crude products were purified by
9.14 (s, 4H, PyzH), 8.26 (t, 4H, J = 6.0 Hz, NH), 6.75 (s, 8H, ArH), numerous crystallizations from CH2Cl2–hexane affording the
4.92–4.80 (m, 8H, CH(CH3)2), 4.36 (d, 4H, J = 12.4 Hz, ArCH2Ar), desired compounds as pale yellow powders.
c
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013
New J. Chem., 2013, 37, 391--402 399