Halogenation of Cubane under Phase-Transfer Conditions
J. Am. Chem. Soc., Vol. 123, No. 9, 2001 1847
dried over Na2SO4; excess CH2Cl2 was removed at atmospheric
pressure. Column chromatography (silica/pentane) gave 20 mg of 1
and 274 mg (75%) of bromocubane (4) identical to the material
described earlier by NMR57,58 and MS59 data.
B. Iodination of Cubane (1). A mixture of 208 mg (2 mmol) of 1,
1.6 g (4 mmol) of HCI3, 5 mL of CH2Cl2, and 3 g of solid NaOH was
stirred at room temperature for 36 h, then diluted with 10 mL of CH2-
Cl2 and filtered; the solid was washed with CH2Cl2 and the solvent
removed at atmospheric pressure. The residue was separated by column
chromatography (silica/pentane): 25 mg of cubane 1 were recovered;
308 mg (67%) of iodocubane 5 were isolated. The material was identical
to that described earlier by NMR60 data. MS m/z (%) 230 (1), 204 (4),
127 (22), 103 (40), 77 (100), 51 (33).
C. Chlorination of Cubane (1). A mixture of 208 mg (2 mmol) of
1, 15 mL of CCl4, 5 mL of 50% aqueous NaOH, and 25 mg of
tetrabutylammonium bromide was stirred under reflux for 5 days,
diluted with 10 mL of water, and extracted with CCl4 (3 × 5 mL). The
extracts were washed with water and dried over Na2SO4, and excess
CCl4 was removed at atmospheric pressure with use of a Vigreux
column. Separating by column chromatography (silica/pentane) gave
10 mg of 1 and 227 mg (81%) of chlorocubane 6, which was identical
to the material described earlier by MS12 data. 1H NMR: 4.18 (m, 3H),
4.03 (m, 4H). 13C NMR: 72.76, 56.69, 48.22, 43.87. Mp ) 28-29
°C.
D. Bromination of Bromocubane (4). A mixture of 183 mg (1
mmol) of 4, 640 mg (2 mmol) of CBr4, 3 mL of CH2Cl2, 1.5 mL of
50% aqueous NaOH, and 10 mg of tetrabutylammonium bromide was
allowed to react following procedure A (5 days); after column
chromatography, 25 mg of 4 was recovered and 183 mg (65%) of a
mixture of 1,2- (7), 1,3- (8), and 1,4- (9) dibromocubanes was obtained
in a ratio of 7:8:9 ) 0.63:1.00:0.09 according to GC/MS and NMR
data. 1,2-Dibromocubane (7): 1H NMR δ 4.34 (m, 4H), 4.19 (m, 2H);
13C NMR δ 67.9, 55.11, 46.19; MS m/z (%) 262 (0.5%), 236 (1%),
182 (2%), 156 (5%), 102 (100%), 76 (10%), 50 (8%). 1,3-Dibromocu-
bane (8): 1H NMR δ 4.47 (m, 2H), 4.11 (m, 2H), 4.18 (m, 2H); 13C
NMR δ 65.25, 58.27, 57.41, 43.18; MS m/z (%) 262 (0.4%), 236 (2%),
182 (2%), 156 (5%), 102 (100%), 76 (8%), 50 (6%). 1,4-Dibromocu-
bane was identical to the material described earlier by NMR data.32,58
E. Iodination of Iodocubane (5). A mixture of 115 mg (0.5 mmol)
of iodocubane 5, 0.79 g (2 mmol) of HCI3, 5 mL of CH2Cl2, and 1.5
g of solid NaOH was stirred at room temperature for 3 days; then the
reaction mixture was filtered and an additional amount of 0.79 g (2
mmol) of HCI3, 3 mL of CH2Cl2, and 1.5 g of solid NaOH was added
to the reaction mixture. After another 5 days of stirring, the reaction
mixture was worked up as in B; 16 mg of 5 were recovered and 123
mg (69%) of a mixture of 1,2- (10), 1,3- (11), and 1,4- (12)
diodocubanes was obtained in a ratio of 10:11:12 ) 0.70:1.00:0.08
according to GC/MS and NMR data. 1,2-Diiodocubane (10):61 1H NMR
δ 4.43 (m); 13C NMR δ 57.45, 48,72, 45.94; MS m/z (%) 228 (0.3%),
204 (3%), 127 (2%), 102 (100%), 76 (14%), 50 (9%). 1,3-Diiodocubane
(11): 1H NMR δ 4.46 (m, 4H), 4.33 (m, 2H); 13C NMR δ 65.80, 57.69,
48.76, 32.21; MS m/z (%) 228 (0.5%), 204 (4%), 127 (6%), 102 (100%),
76 (16%), 50 (12%). 1,4-Diiodocubane (12) was identical to the material
described earlier by NMR and MS data.58,62
chromatography, was obtained 35 mg of unreacted 6 and 95 mg (55%)
of a mixture of 1,2- (13), 1,3- (14), and 1,4- (15) dichlorocubanes in
a ratio of 13:14:15 ) 0.70:1.00:0.09 identified according to GC/MS
and NMR data. 1,2-Dichlorocubane (13): 1H NMR δ 4.17 (m, 4H),
4.03 (m, 2H); 13C NMR δ 69.94, 53.35, 44.53; MS m/z (%) 172 (0.3%,
137 (12%), 112 (19%), 102 (100%), 75 (21%), 50 (14%). 1,3-
Dichlorocubane (14): 1H NMR δ 4.32 (m, 2H), 4.17 (m, 2H), 4.03
(m, 2H); 13C NMR δ 67.53, 64.59, 56.93, 39.67; MS m/z (%) 172
(0.7%), 146 (18%), 136 (21%), 112 (27%), 102 (100%), 75 (38%), 51
(23%). 1,4-Dichlorocubane (15) was identical to NMR and MS literature
data.32
G. Iodination of Bromocubane (4). From 183 mg (1 mmol) of
bromocubane 4, following procedure E (4 days), 53 mg of unreacted
4 and 151 mg (49%) of a mixture of 1,2- (16), 1,3- (17), and 1,4- (18)
iodobromocubanes was obtained in a ratio of 16:17:18 ) 0.68:1.00:
0.09 according to GC/MS and NMR data. 1-Iodo-2-bromocubane
(16): 1H NMR δ 4.42 (m, 2H), 4.35 (m, 2H), 4.30 (m, 2H); 13C NMR
δ 57.25, 54.94, 53.10, 48.64, 45.99, 45.22; MS m/z (%) 310 (0.3%),
282 (1%), 228 (2%), 204 (4%), 156 (5%), 127 (8%), 102 (100%), 76
(10%), 50 (7%). 1-Iodo-3-bromocubane (17): 1H NMR δ 4.48 (m, 2H),
4.27 (m, 2H), 4.22 (m, 2H); 13C NMR δ 65.59, 60.55, 57.72, 57.24,
46.01, 30.09; MS m/z (%) 282 (0.8%), 228 (0.5%), 204 (2%), 156 (3%),
127 (6%), 102 (100%), 76 (9%), 50 (4%). 1-Iodo-4-bromocubane (18)
was described previously:63 13C NMR δ 63.37, 57.00, 54.81, 31.12;
MS m/z (%) 282 (0.8%), 228 (0.5%), 204 (2%), 156 (3%), 127 (6%),
102 (100%), 76 (9%), 50 (4%).
H. Bromination of Chlorocubane (6). From 137 mg (1 mmol) of
chlorocubane 6, following procedure D (4 days), 17 mg of unreacted
6 and 154 mg (71%) of a mixture of 1,2- (19), 1,3- (20), and 1,4- (21)
bromochlorocubanes was obtained. The ratio of 19:20:21 ) 0.67:1.00:
0.09 according to GC/MS and NMR data. 1-Bromo-2-chlorocubane
(19): 1H NMR δ 4.26 (m, 4H), 4.12 (m, 2H); 13C NMR δ 67.94, 54.99,
53.60, 53.43, 46.47, 44.42; MS m/z (%) 216 (0.3%), 192 (3%), 156
(5%), 136 (7%), 112 (9%), 102 (100%), 75 (18%), 51 (11%). 1-Bromo-
3-chlorocubane (20): 1H NMR δ 4.01 (m, 2H), 4.23 (m, 2H), 4.10 (m.
2H); 13C NMR δ 68.77, 64.99, 57.56, 57.48, 56.74, 41.49; MS m/z
(%) 216 (0.2%), 192 (4%), 156 (6%), 136 (5%), 112 (8%), 102 (100%),
75 (15%), 51 (10%). 1-Bromo-4-chlorocubane (21) was identical to
NMR and MS spectra described previously.12
M. Iodination of Chlorocubane (6). From 137 mg (1 mmol) of
chlorocubane 6, following procedure E, 50 mg of unreacted 6 and 143
mg (54%) of a mixture of 1,2- (22), 1,3- (23), and 1,4- (24)
iodochlorocubanes was obtained in a ratio of 22:23:24 ) 0.65:1.00:
0.09 according to GC/MS and NMR data. 1-Iodo-2-clorocubane (22):
1H NMR δ 4.33 (2H), 4.23 (m, 2H), 4.18 (m, 2H); 13C NMR δ 74.82,
57.12, 53.23, 48.85, 45.04, 44.87; MS m/z (%) 264 (0.3%), 228 (0.7%),
204 (2%), 127 (7%), 102 (100%), 75 (21%), 51 (12%). 1-Iodo-3-
chlorocubane (23): 1H NMR δ 4.41 (m, 2H), 4.29 (m, 2H), 4.14 (m,
2H); 13C NMR δ 70.68, 65.27, 57.96, 56.72, 44.25, 29.07; MS m/z
(%) 238 (1%), 204 (3%), 127 (5%), 112 (6%), 102 (100%), 75 (21%),
51 (12%). 1-Iodo-4-chlorocubane (24) was prepared previously:18 13
C
NMR δ 70.62, 56.58, 53.15, 29.18; MS m/z (%) 238 (1%), 204 (3%),
127 (5%), 112 (6%), 102 (100%), 75 (21%), 51 (12%).
F. Chlorination of Chlorocubane (6). From 137 mg (1 mmol) of
chlorocubane 6, following procedure C (10 days) after column
Acknowledgment. This work was supported by the Volk-
swagenstiftung (Grant I/74614). We are grateful to the HRLS
(Stuttgart) for generous allotments of computer time. P.R.S.
thanks the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie as well as Prof. Dr. A. de Meijere for
continuing support.
(56) The reaction conditions were not optimized. A substantial shortening
of the reaction times for the bromination and iodination of cubanes was
observed at higher temperatures.
(57) Edward, J. T.; Farrell, P. G.; Langford, G. E. J. Am. Chem. Soc.
1976, 98, 3075-3085.
(58) Axenrod, T.; Liang, B.; Bashir-Hashemi, A.; Dave, P. R.; Reddy,
D. S. Magn. Reson. Chem. 1991, 29, 88-91.
Supporting Information Available: Tables with absolute
energies, including ZPVEs, as well as thermal corrections to
enthalpies and xyz-coordinate energies of all computed species
and Figures 4S and 5S depicting ground and transition structures
for different halogenation reactions described in the present work
(PDF). This material is available free of charge via the Internet
(59) Luh, S. J. Org. Chem. 1977, 42, 2790.
(60) Abeywickrema, R. S.; Della, E. W. J. Org. Chem. 1980, 45, 4226-
4229.
(61) 1,2-Diiodocubane was first prepared by Eaton et al. (Eaton, P. E.;
Maggini, M. J. Am. Chem. Soc. 1988, 110, 7230-7232), but was not
separated from byproducts.
(62) Reddy, D. S.; Sollot, G. P.; Eaton, P. E. J. Org. Chem. 1989, 54,
722-723.
(63) Moriarty, R. M.; Khosrowshahi, J. S.; Dalecki, T. M. Chem.
Commun. 1987, 675-676.
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