LETTER
Regioselective Synthesis of Substituted [2.2]Paracyclophanes
2133
Data for compounds 13b: highly hygroscopic solid. 1H NMR
(D2O): d = 2.33 (3 H, s, ArCH3), 3.11 and 3.16 [total 9 H, s,
N(CH3)3], 4.46 and 4.62 (total 2 H, s, ArCH2), 7.30–7.72
(total 3 H, m, ArH). 13C NMR (D2O): d = 21.4, 23.3, 53.3,
53.8, 68.4, 68.6, 124.9, 125.6, 127.5, 127.7, 130.0, 132.3,
132.8, 135.0, 135.8, 136.7, 141.3, 144.3. MS (FAB):
m/z (%) = 242 (100) [M – Br]+. HRMS: m/z calcd for
C11H17N79Br: 242.0539; found: 242.0540.
Acknowledgment
We thank the Innovation and Technology Commission of the HK-
SAR and Varitronix Limited for the financial support (UIM/78).
References
(1) Bartholomew, G. P.; Bazan, G. C. Acc. Chem. Res. 2001, 34,
30.
(2) (a) Morisaki, Y.; Chujo, Y. Macromolecules 2002, 35, 587.
(b) Morisaki, Y.; Chujo, Y. Chem. Lett. 2002, 194.
(c) Morisaki, Y.; Ishida, T.; Chujo, Y. Macromolecules
2002, 35, 7872.
(3) Salhi, F.; Collard, D. M. Adv. Mater. 2003, 15, 81.
(4) Gibson, S. E.; Knight, J. D. Org. Biomol. Chem. 2003, 1,
1256.
(5) (a) Acetylation: Cram, D. J.; Allinger, N. J. J. Am. Chem.
Soc. 1955, 77, 6289. (b) Bromination: Cram, D. J.; Day, A.
C. J. Org. Chem. 1966, 31, 1227. (c) Carbomethoxylation:
Zitt, H.; Dix, I.; Hopf, H.; Jones, P. G. Eur. J. Org. Chem.
2002, 2298. (d) Formylation: Banfi, S.; Manfredi, A.;
Montanari, F.; Pozzi, G.; Quici, S. J. Mol. Catal. A: Chem.
1996, 133, 77. (e) Nitration: Lahann, J.; Höcker, H.; Langer,
R. Angew. Chem. Int. Ed. 2001, 40, 726.
(6) (a) Brink, M. Synthesis 1975, 807. (b) Cipiciani, A.;
Fringuelli, F.; Mancini, V.; Piermatti, O.; Pizzo, F.;
Ruzziconi, R. J. Org. Chem. 1997, 62, 3744. (c) Marshall,
J. L.; Hall, L. Tetrahedron 1981, 37, 1271. (d) Rozenberg,
V.; Dubrovina, N.; Sergeeva, E.; Antonov, D.; Belokon, Y.
Tetrahedron: Asymmetry 1998, 9, 653. (e) Minuti, L.;
Taticchi, A.; Marrocchi, A. Tetrahedron: Asymmetry 2000,
11, 4221.
Data for compound 13e: mp >230 °C (dec.). 1H NMR (D2O):
d = 2.37 (3 H, s, ArCH3), 3.18 [9 H, s, N(CH3)3], 4.63 (2 H,
s, ArCH2), 7.68 (1 H, s, ArH), 7.81 (1 H, s, ArH). 13C NMR
(D2O): d = 22.7, 53.6, 67.8, 124.5, 126.3, 126.9, 136.3,
138.3, 144.0. MS (FAB) m/z (%) = 322 (80) [M – Br]+.
HRMS: m/z calcd for C11H16N79Br2: 319.9644; found:
319.9636.
Data for compound 13g: mp >230 °C (dec.). 1H NMR
(D2O): d = 2.52 (3 H, s, ArCH3), 3.10 [9 H, s, N(CH3)3], 4.44
(2 H, s, ArCH2), 7.74 (2 H, s, ArH). 13C NMR (D2O): d =
23.8, 53.1, 60.2, 68.3, 125.8, 128.2, 136.2, 141.2. MS
(FAB): m/z (%) = 322 (70) [M – Br]+. HRMS: m/z calcd for
C11H16N79Br2: 319.9644; found: 319.9652.
Data for compound 13h: mp >210 °C (dec.). 1H NMR
(DMSO-d6): d = 2.85 (3 H, s, ArCH3), 3.26 [9 H, s,
N(CH3)3], 5.15 (2 H, s, ArCH2). 13C NMR (DMSO-d6):
d = 29.8, 54.1, 71.3, 129.3, 130.1, 131.4, 144.3. MS (FAB)
m/z (%) = 480 (100) [M – Br]+. HRMS: m/z calcd for
C11H14N79Br4: 475.7854; found: 475.7848.
(13) Synthesis of Substituted 4-Methylbenzyl Bromides 12
from Substituted p-Xylenes.
A mixture of the substituted p-xylenes (ca. 10 g), N-
bromosuccinimide (1 equiv) and benzoyl peroxide (0.01 g)
in CCl4 (100 mL) was heated to reflux. After 3 h, the reaction
mixture was cooled to 0 °C and the precipitated succinimide
was removed by filtration and washed with CHCl3. The
combined filtrates were evaporated under reduced pressure
to give an oil that was purified by flash chromatography on
silica gel (eluent: hexane) to afford the bromides 12 as a
single compound or a regioisomeric mixture.
(7) (a) Reich, H. J.; Cram, D. J. J. Am. Chem. Soc. 1969, 91,
3505. (b) Reich, H. J.; Cram, D. J. J. Am. Chem. Soc. 1969,
91, 3527. (c) Yeh, Y. L.; Gorham, W. F. J. Org. Chem. 1969,
34, 2366. (d) König, B.; Knieriem, B.; de Meijere, A. Chem.
Ber. 1993, 126, 1643. (e) Bartholomew, G. P.; Bazan, G. C.
J. Am. Chem. Soc. 2002, 124, 5183.
Data for 12b: colorless oil; Rf = 0.68 (hexane). 1H NMR
(CDCl3): d = 2.32 and 2.38 (total 3 H, s, ArCH3), 4.41 and
4.58, (total 2 H, s, ArCH2Br), 7.07–7.56 (total 3 H, m, ArH).
13C NMR (CDCl3): d = 20.8, 22.6, 32.1, 33.5, 124.2, 124.8,
127.8, 128.7, 130.9, 131.0, 132.6, 133.7, 133.9, 137.0,
138.1, 140.5. MS (EI): m/z (%) = 264 (23) [M+]. HRMS:
m/z calcd for C8H879Br2: 261.8987; found: 261.8990. Anal.
Calcd for C8H8Br2: C, 36.40; H, 3.05. Found: C, 36.16; H,
2.97.
(8) (a) Winberg, H. E.; Fawcett, F. S.; Mochel, W. E.; Theobald,
C. W. J. Am. Chem. Soc. 1960, 82, 1428. (b) Winberg, H.
E.; Fawcett, F. S. Org. Synth., Coll. Vol. V; John Wiley and
Sons, Ltd.: New York, 1973, 883–886.
(9) (a) Cram, D. J.; Dalton, C. K.; Knox, G. R. J. Am. Chem. Soc.
1963, 85, 1088. (b) Longone, D. T.; Chow, H. S. J. Am.
Chem. Soc. 1964, 86, 3898. (c) Brown, G. W.; Sondheimer,
F. J. Am. Chem. Soc. 1967, 89, 7116. (d) Hopf, H. Angew.
Chem., Int. Ed. Engl. 1972, 5, 419. (e) Otsubo, T.; Horita,
H.; Misumi, S. Synth. Commun. 1976, 6, 591.
Data for 12f: colorless oil; Rf = 0.65 (hexane). 1H NMR
(CDCl3): d = 2.35 (3 H, s, ArCH3), 4.51 (2 H, s, ArCH2), 7.26
(1 H, s, ArH), 7.41 (1 H, s, ArH). 13C NMR (CDCl3): d =
19.7, 29.5, 131.2, 131.9, 132.1, 133.0, 134.2, 138.3. MS
(EI): m/z (%) = 254 (50) [M+]. HRMS: m/z calcd for
C8H779Br35Cl2: 251.9103; found: 251.9110. Anal. Calcd for
C8H7BrCl2: C, 37.84; H, 2.78. Found: C, 37.78; H, 2.91.
(14) Synthesis of Substituted 4-Methylbenzyl Bromides 12
from Substituted 4-Methylbenzyl Alcohols.
(10) Longone, D. T.; Reetz, M. T. J. Chem. Soc., Chem.
Commun. 1967, 46.
(11) (a) Szwarc, M. J. Chem. Phys. 1948, 16, 128. (b) Errede, L.
A.; Landrum, B. F. J. Am. Chem. Soc. 1957, 79, 4952.
(c) Errede, L. A.; Hoyt, J. M. J. Am. Chem. Soc. 1960, 82,
436. (d) Errede, L. A.; Gregorian, R. S.; Hoyt, J. M. J. Am.
Chem. Soc. 1960, 82, 5218.
(12) Typical Procedure for the Preparation of Substituted (4-
Methylbenzyl)trimethylammonium Bromides 13.
In a 250-mL three-necked flask equipped with a stirrer, a gas
outlet connected to an acid trap, and a gas inlet tube directed
to about 1 cm above the surface of the liquid was placed a
solution of the substituted benzyl bromide 12 (ca. 10 g) in
Et2O (100 mL). The flask was cooled in an ice-water bath
with stirring. Et3N was generated by heating an aqueous
solution of Et3N (45% w/w, 50 mL) and passed into the inlet
tube for 2 h. The product began to precipitate as a white
solid. The resulting mixture was then allowed to stand
overnight at r.t. and the ammonium salt 13 was collected on
a Büchner funnel and dried under reduced pressure.
A mixture of the substituted 4-methylbenzyl alcohol (30
mmol), CBr4 (14.92 g, 45 mmol) and PPh3 (11.80 g, 45
mmol) was stirred in THF at r.t. for 4 h. The reaction mixture
was filtered through Celite and the filtrate was concentrated
on a rotary evaporator. The crude product was purified by
flash chromatography on silica gel (eluent: hexane) to give
the target bromide.
Data for 12d: white solid, mp 43–45 °C; Rf = 0.75 (hexane).
1H NMR (CDCl3): d = 2.25 (6 H, s, ArCH3), 4.47 (2 H, s,
ArCH2Br), 7.11–7.17 (3 H, m, ArH). 13C NMR (CDCl3): d =
19.5, 19.7, 33.9, 126.4, 130.0, 130.3, 135.2, 137.1. MS (CI):
m/z (%) = 198 (23) [M+]. HRMS: m/z calcd for C9H1179Br:
Synlett 2005, No. 14, 2130–2134 © Thieme Stuttgart · New York