M.A. Kliachyna et al. / Tetrahedron 65 (2009) 7085–7091
7089
3.42–3.53 (dþm, 3H, ArCH2þCH3CH2CH2O), 3.72–4.00 (m, 6H,
Monobrominated calixarene 4b obtained from 3b. Yield 1.35 g
2
ArCH2þCH3CH2CH2OþNHC(O)CH2), 4.33 (d, 1H, JHH¼12.6 Hz,
(94%). Mp¼221–222 ꢀC. 1H NMR (CDCl3),
d
: 0.82 (t, 3H, 3JHH¼7.4 Hz,
2
ArCH2), 4.70 (d, 1H, JHH¼15.0 Hz, NHC(O)CH2), 5.16–5.26 (m, 1H,
CH3CH2CH2O),
1.51–1.64
(dþm,
3Hþ2H,
3JHH¼7.1 Hz,
3
2
CH3(Ph)CHNH), 6.08 (t, 1H, JHH¼7.5 Hz, ArH), 6.18 (t, 1H,
CH3(Ph)CHNHþCH3CH2CH2O), 3.06 (d, 1H, JHH¼12.6 Hz, ArCH2),
3.39 (d, 1H, 2JHH¼13.8 Hz, ArCH2), 3.56–3.64 (m, 1H, CH3CH2CH2O),
3.71–3.99 (m, 7H, ArCH2þCH3CH2CH2OþOCH2CONH), 4.10 (d, 1H,
2JHH¼12.8 Hz, ArCH2), 4.66 (d, 1H, 2JHH¼14.9 Hz, OCH2CONH), 5.22–
3JHH¼7.5 Hz, ArH), 6.41–6.50 (m, 4H, ArH), 6.63 (t, 2H, 3JHH¼7.7 Hz,
3
ArH), 6.75–6.81 (m, 2H, ArH), 6.86 (t, 1H, JHH¼7.5 Hz, ArH), 7.13–
7.38 (m,11H, ArH), 7.77 (s,1H, OH), 8.22 (d,1H, 3JHH¼7.9 Hz, NH). 13
C
3
NMR (CDCl3),
d
: 9.65, 22.20, 22.43, 31.14, 31.49, 37.74 (2C), 48.08,
5.31 (m, 1H, CH3(Ph)CHNH), 6.13 (t, 1H, JHH¼7.3 Hz, ArH), 6.27 (t,
3
3
71.38, 75.62, 119.78, 123.95, 124.80, 125.30, 126.00, 126.86, 126.91,
127.11, 127.90, 128.24, 128.53, 128.63, 128.77, 128.91, 129.07, 129.12,
129.57, 129.71, 129.80, 129.91, 132.21, 132.30, 132.38, 132.54, 132.87,
133.21, 143.10, 148.01, 152.10, 152.31, 154.46, 163.26, 168.85. Anal.
Found: C, 78.67%; H, 6.25%; N, 1.96%. Calcd for C48H45NO6: C,
78.77%; H, 6.20%; N, 1.91%.
1H, JHH¼7.3 Hz, ArH), 6.43 (d, 1H, JHH¼7.2 Hz, ArH), 6.49 (d, 1H,
3JHH¼7.3 Hz, ArH), 6.56–6.58 (m, 2H, ArH), 6.69–6.78 (m, 3H, ArH),
3
6.82 (d, 1H, JHH¼7.3 Hz), 7.11–7.13 (m, 3H, ArH), 7.18–7.22 (m, 1H,
ArH), 7.28–7.36 (m, 7H, ArH), 7.77 (s, 1H, OH), 7.98 (d, 1H,
3JHH¼8.7 Hz, NH). 13C NMR (CDCl3),
d: 9.93, 21.95, 22.71, 30.94,
31.31, 37.73, 37.75, 47.97, 71.51, 75.70, 78.98, 111.16, 120.85, 124.12,
125.10, 126.02, 127.27, 128.02, 128.38, 128.41, 128.70, 128.76, 128.80,
128.89, 128.96, 129.07, 129.17, 129.28, 129.41, 129.77, 130.04, 130.19,
130.42, 131.09, 131.87, 132.09, 132.45, 132.58, 132.69, 133.29, 134.19,
142.92, 148.16, 149.17, 151.66, 152.21, 154.47, 163.35, 168.43. Anal.
Found: C, 70.86%; H, 5.14%; N, 1.93%; Br, 9.77%. Calcd for
C48H44BrNO6: C, 71.11%; H, 5.47%; N, 1.73%; Br, 9.86%.
4.3.3. Diastereomer 3b
3
Mp¼218–219 ꢀC. 1H NMR (CDCl3),
d
: 0.82 (t, 3H, JHH¼7.4 Hz,
3
CH3CH2CH2O), 1.52 (d, 3H, JHH¼7.2 Hz, CH3(Ph)CHNH), 1.56–1.66
3
2
(m, 2H, JHH¼7.4 Hz, CH3CH2CH2O), 3.13 (d, 1H, JHH¼12.8 Hz,
2
ArCH2), 3.45 (d, 1H, JHH¼13.7 Hz, ArCH2), 3.58–3.66 (m, 1H,
3JHH¼7.2 Hz,
CH3CH2CH2O),
3.70–3.99
(m,
7H,
ArCH2
-
2
þCH3CH2CH2OþNHC(O)CH2), 4.16 (d, 1H, JHH¼12.8 Hz, ArCH2),
4.5. Removal of benzoyl group of calixarene 4a
2
4.66 (d, 1H, JHH¼15.1 Hz, NHC(O)CH2), 5.21–5.30 (m, 1H,
3
CH3(Ph)CHNH), 6.07 (t, 1H, JHH¼7.5 Hz, ArH), 6.21 (t, 1H,
To the ethanol/water (3.5 mL of EtOH and 2 mL of H2O) solution
of KOH (0.48 g, 8.53 mmol) the solution of calixarene 3a (0.230 g,
2.84 mmol) in THF (5 mL) was added. The reaction mixture was
refluxed for 5 h. After the removal of solvent under reduced pres-
sure, 10 mL of 3% solution of HCl and 1 mL of EtOH were added. The
precipitated product was filtered off, washed with water and dried
in the air. Yield of 5, 0.19 g (95%). Mp¼139–140 ꢀC. 1H NMR (CDCl3),
3JHH¼7.5 Hz, ArH), 6.40 (d, 1H, JHH¼7.5 Hz, ArH), 6.46 (d, 1H,
3
3JHH¼7.5 Hz, ArH), 6.52–6.54 (m, 2H, ArH), 6.63–6.71 (m, 3H, ArH),
6.80–6.88 (m, 2H, ArH), 7.08–7.23 (m, 7H, ArH), 7.27–7.35 (m, 4H,
ArH), 7.64 (s, 1H, OH), 8.12 (d, 1H, JHH¼8.3 Hz, NH). 13C NMR
3
(CDCl3), d: 10.11, 22.24, 22.83, 31.36, 31.68, 37.90, 37.92, 48.12, 71.58,
75.74, 77.20, 119.62, 123.82, 124.74, 125.18, 125.92, 126.69, 126.81,
127.06, 128.59, 128.69, 128.73, 129.11, 129.19, 129.59, 129.71, 129.73,
129.99, 132.18, 132.20, 132.31, 132.41, 132.57, 132.86, 133.23, 142.96,
148.07, 152.22, 152.28, 154.31, 163.09, 168.28. Anal. Found: C,
78.56%; H, 6.27%; N,1.99%. Calcd for C48H45NO6: C, 78.77%; H, 6.20%;
N, 1.91%.
3
3
d
: 0.98 (t, 3H, JHH¼7.4 Hz, CH3CH2CH2), 1.67 (d, 3H, JHH¼7.0 Hz,
3
CH3(Ph)CHNH), 1.74–1.88 (m, 2H, JHH¼7.5, 7.2 Hz, CH3CH2CH2O),
2
3.30–3.44 (4d overlapping, 4H, JHH¼13.8, 13.2, 13.6, 13.2 Hz,
ArCH2eq), 3.79–3.93 (m, 2H, CH3CH2CH2O), 4.13 (d, 1H,
2JHH¼13.6 Hz, ArCH2ax), 4.16 (d, 1H, 2JHH¼13.2 Hz, ArCH2ax), 4.17 (d,
1H, 2JHH¼13.8 Hz, ArCH2ax), 4.2 (d, 1H, 2JHH¼13.2 Hz, ArCH2ax), 4.42
2
2
(d, 1H, JHH¼15.1 Hz, OCH2CONH), 4.56 (d, 1H, JHH¼15.1 Hz,
OCH2CONH), 5.27–5.37 (m, 1H, CH3(Ph)CHNH), 6.54–6.62 (m, 2H,
ArH), 6.72–6.81 (m, 5H, ArH), 7.06–7.11 (m, 2H, ArH), 7.19–7.23 (m,
5H, ArH), 7.39–7.41 (m, 2H, ArH), 7.43 (s, 1H, OH), 7.64 (s, 1H, OH),
4.4. Bromination of calixarenes 3a and 3b with N-
bromosuccinimide (NBS)
4.4.1. General procedure
8.72 (d, 1H, 3JHH¼7.9 Hz, NH). 13C NMR (CDCl3),
d: 10.40, 17.14, 22.19,
To a solution of calixarene (1.30 g,1.78 mmol) in acetone (50 mL,
freshly distilled) the solution of NBS (0.33 g, 1.87 mmol) in 50 mL of
acetone was added dropwise. The reaction mixture was stirred for
18 h at 20 ꢀC. After removal of acetone under reduced pressure the
residue was treated with 5 mL of MeOH and 20 mL of H2O. The
colourless precipitate was filtered off, washed with water and dried
in the air.
23.10, 31.11, 31.31, 31.39, 31.58, 48.73, 74.55, 78.91, 111.07, 119.78,
125.47, 125.99, 126.17, 127.08, 127.71, 127.76, 128.41, 128.71, 128.89,
129.09, 129.18, 129.34, 129.61, 129.75, 130.14, 131.02, 131.04, 131.59,
131.95, 132.62, 132.73, 143.10, 151.70, 151.99, 152.54, 167.49. Anal.
Found: C, 69.91%; H, 5.63%; N, 1.87%; Br, 11.02%. Calcd for
C41H40BrNO5: C, 69.69%; H, 5.71%; N, 1.98%; Br, 11.31%.
Monobrominated calixarene 4a obtained from 3a. Yield 1.38 g
4.6. Removal of phenylethylamide auxiliary group of
calixarene 5
(97%). Mp¼231–232 ꢀC. 1H NMR (CDCl3),
d
: 0.54 (t, 3H, 3JHH¼7.5 Hz,
CH3CH2CH2O), 1.14–1.33 (m, 2H, CH3CH2CH2O), 1.46 (d, 3H,
3JHH¼7.0 Hz, CH3(Ph)CHNH), 3.26 (d, 1H, 2JHH¼12.8 Hz, ArCH2), 3.38
(d, 1H, 2JHH¼13.8 Hz, ArCH2), 3.42–3.51 (m, 1H, CH3CH2CH2O), 3.71–
3.98 (m, 7H, ArCH2þCH3CH2CH2OþOCH2CONH), 4.29 (d, 1H,
2JHH¼12.8 Hz, ArCH2), 4.69 (d, 1H, 2JHH¼15.2 Hz, OCH2CONH), 5.16–
To the ethanol/water (4 mL of EtOH, 6 mL of H2O) solution of
KOH (6.42 g, 114.62 mmol) calixarene 5 (0.54 g, 7.64 mmol) was
added. The reaction mixture was refluxed for 120 h. The 10% solu-
tion of HCl (30 mL) was added at stirring, then mixture was
refluxed for 1.5 h. The precipitate was filtered off, washed with
large amounts of hot water and dried in the air. The product was
extracted from the solid with 30 mL of hot CHCl3. The crude
product was purified by column chromatography using ethyl ace-
3
5.26 (m, 1H, CH3(Ph)CHNH), 6.14 (t, 1H, JHH¼7.5 Hz, ArH), 6.24 (t,
3
1H, JHH¼7.5 Hz, ArH), 6.43–6.54 (m, 4H, ArH), 6.70–6.82 (m, 4H,
ArH), 7.11–7.16 (m, 1H, ArH), 7.24–7.39 (m, 10H, ArH), 7.91 (s, 1H,
OH), 8.09 (d, 1H, 3JHH¼7.9 Hz, NH). 13C NMR (CDCl3),
d: 9.69, 22.10,
22.44, 30.96, 31.35, 37.78 (2C), 48.13, 71.55, 75.75, 111.23, 124.17,
125.06, 125.35,126.10,126.98, 127.22,128.04, 128.30, 128.74,129.03,
129.08, 129.30, 129.78, 129.97, 130.17, 130.50, 131.15, 131.81, 131.86,
132.09, 132.43, 132.62, 132.69, 133.30, 143.15, 148.16, 151.67, 152.15,
154.59,163.24,168.62. Anal. Found: C, 70.86%; H, 5.14%; N,1.93%; Br,
9.66%. Calcd for C48H44BrNO6: C, 71.11%; H, 5.47%; N, 1.73%; Br,
9.86%.
tate/hexane 1:1 as eluent. Yield of 6a 0.22 g (48%). Mp¼298–
20
300 ꢀC. [
a
]
ꢁ5.5 (c 0.5083 g/100 mL, CHCl3). 1H NMR (CDCl3),
d:
D
1.25 (t, 3H, 3JHH¼7.2 Hz, CH3CH2CH2), 2.06–2.17 (m, 2H, 3JHH¼7.2 Hz,
2
CH3CH2CH2O), 3.39–3.49 (dþd, 2Hþ1H, JHH¼13.6, 13.4 Hz,
2
ArCH2eq), 3.50 (d, 1H, JHH¼13.4 Hz, ArCH2eq), 4.01–4.10 (tþd,
3
2
2Hþ2H, JHH¼6.7 Hz, JHH¼13.6 Hz, CH3CH2CH2OþArCH2ax), 4.15–
2
4.21 (dþd, 1Hþ1H, JHH¼13.4 Hz, ArCH2ax), 4.61 (d, 1H,