5950
S. M. Ahmad et al. / Tetrahedron Letters 48 (2007) 5948–5952
contrast, the stoichiometric reaction of benzamidine 21
with NBS in carbon tetrachloride gave N-bromoamidine
229,§ as yellow needles suitable for X-ray crystallography
(Fig. 1). The solid state structure revealed the presence
of two crystallographically independent molecules A
and B (molecule A is shown in Fig. 1, and molecule B
in Fig. S1 in the electronic Supplementary data). The
˚
two N–Br bond lengths [1.9002(18) A in molecule A,
˚
and 1.9087(18) A in molecule B] are slightly longer than
those seen in other literature species with C@N–Br
moieties, though there are so few that the comparisons
must be made with caution.10 This is the first time that
a N-bromoamidine has been characterised crystallo-
graphically.–
Figure 1. The molecular structure of one (A) of the two crystallo-
graphically independent molecules present in the crystals of 22.
Br
Ph
NH
NH2
N
Br
N
N
NH2
Ph
Ph
When a catalytic quantity (10 mol %) of N-bromoami-
dine 22 was added instead, a quantitative conversion
to brominated product 24 was also obtained after 3 h.
These experiments demonstrate conclusively that (pro-
tonated) N-bromoamidine 22 is an intermediate in the
catalytic cycle (Scheme 1).
20
21
22
Isolated, pure N-bromoamidine 22 (1.0 equiv) proved to
act as a stoichiometric electrophilic bromine donor
when allowed to react with trans-anethole 23 (1.0 equiv)
and acetic acid (4.0 equiv) giving 50% conversion to bro-
moacetate 24k in 10 min, with benzamidine 21 as the
only other detectable product. Benzamidine 21 itself
was found to act as a catalyst (10 mol %) for the
same bromination reaction with stoichiometric NBS
(1.0 equiv) with quantitative conversion to 24 after 3 h.
OAc
Br
MeO
MeO
23
24
Having defined the nature of the catalytic intermediate,
the possibility of performing asymmetric bromoacetoxyl-
ation or bromolactonisation using a chiral amidine was
explored. Enantiopure (R,R)-iso-amarine 5,11 novel
planar-chiral [2.2]paracyclophane amidine 25 and novel
C3-symmetric amidine 26 were selected as potential
asymmetric catalysts. Amidine 25 was prepared from
the known (S)-4-carboxamido[2.2]paracyclophane12 via
imidate formation followed by treatment with commer-
cially available (R,R)-1,2-diamino-1,2-diphenylethane.
The C3-symmetric amidine 26 was prepared by the
§ Benzamidine 21 (622 mg, 5.2 mmol) was mixed with NBS (920 mg,
5.2 mmol) in CCl4 (15 mL), stirred for 1 h and the reaction mixture
cooled to ꢀ5 ꢁC. The precipitate was filtered off and the filtrate
evaporated to give a crude solid. Recrystallisation yielded the N-
bromoamidine 22 (522 mg, 50%) as yellow needles; mp 73–74 ꢁC (1-
chlorobutane/40–60 ꢁC petroleum ether) [lit.9 81 ꢁC]; IR (KBr disc
cmꢀ1) tmax 3399, 3278, 3148, 1624 cmꢀ1; 1H NMR (CDCl3, 270 MHz)
d 7.59 (m, 2H, ArH), 7.45–7.39 (m, 3H, ArH), 5.67 (br s, 2H, NH2);
13C NMR (CDCl3, 68 MHz) d 164.7, 132.4, 131.1, 128.8, 127.0; MS
(E.I.) m/z 200, 198 [M]+; HRMS calcd for [M]+ C7H7N281Br:
199.9772. Found 199.9773; HRMS calcd for [M]+ C7H7N279Br:
197.9793. Found: 197.9792; Anal. Calcd for C7H7N2Br: C, 42.24; H,
3.54; N, 14.07. Found: C, 42.22; H, 3.45; N, 13.95. Crystal data for 22:
A solution of triethyloxonium tetrafluoroborate (0.8 mL, 1 M,
0.8 mmol) in CH2Cl2 was added to a suspension of (S)-4-carbox-
amido[2.2]paracyclophane (190 mg, 0.8 mmol) in CH2Cl2 and the
mixture stirred for 14 h. Dry EtOH (2 mL) was added, the reaction
stirred for 5 min and (R,R)-1,2-diamino-1,2-diphenylethane (175 mg,
0.8 mmol) added. The reaction was stirred for a further 14 h, diluted
with CH2Cl2 (100 mL) and washed with aqueous NaOH solution
(75 mL, 5% w/v). The organic phase was dried (MgSO4) and
evaporated to give the crude amidine. Column chromatography
yielded the amidine 25 (100 mg, 30%) as a colourless oil; Rf = 0.25–
C7H7BrN2, M = 199.06, monoclinic, P21/c (no. 14), a = 7.7873(4),
3
˚
˚
b = 16.1058(8), c = 12.3914(6) A, b = 92.032(4)ꢁ, V = 1553.16(13) A ,
Z = 8 (2 independent molecules), Dc = 1.703 g cmꢀ3
, l(Mo-
Ka) = 5.215 mmꢀ1, T = 173 K, colourless platy needles, Oxford
Diffraction Xcalibur 3 diffractometer; 5329 independent measured
reflections, F2 refinement, R1 = 0.037, wR2 = 0.076, 3692 independent
observed absorption-corrected reflections [jFoj > 4r(jFoj),
2hmax = 65ꢁ], 197 parameters. CCDC 644181.
– A search of the Cambridge Structural Database (version 5.28, Jan-07
update) failed to find any such structures. For a crystalline bromo-
amidine, that is, also part of a heterocyclic system, see Ref. 10b.
k Data for 24: Colourless oil; Rf = 0.23 (50:50 CH2Cl2/40–60 ꢁC
25
0.50 (50:50 EtOAc:40–60 ꢁC petroleum ether); ½aꢁD +42.0 (c 0.1,
CH2Cl2); IR (thin film) tmax 3385, 3029, 2927, 2856 cmꢀ1; 1H NMR
(CDCl3, 270 MHz) d 7.41–7.28 (m, 10H, ArH), 7.01 (d, J = 1.6 Hz,
1H, H5), 6.83 (d, J = 7.8 Hz, 1H, H7), 6.60–6.50 (m, 5H, ArH), 5.05
(s, 1H, NH), 4.02 (m, 1H, H20), 3.25–2.90 (m, 9H, ArCH2,
PhCHCHPh); 13C NMR (CDCl3, 68 MHz) d 163.7, 144.1, 140.2,
139.7, 139.4, 136.1, 134.7, 132.9, 132.8, 132.7, 131.7, 130.8, 128.8,
127.6, 126.7, 60.0, 35.4, 35.3, 35.2, 31.0; MS (E.I.) m/z 428 [M]+;
HRMS calcd for [M]+ C31H28N2 428.2244. Found: 428.2248. Anal.
Calcd for C31H28N2: C, 86.88; H, 6.59; N, 6.54. Found: C, 86.79; H,
6.56; N, 6.61.
petroleum ether); IR (thin film) tmax 1744 cmꢀ1 1H NMR (CDCl3,
;
270 MHz) d 7.31 (d, J = 7.5 Hz, 2H, ArH), 6.91 (d, J = 7.5 Hz, 2H,
ArH), 5.90 (d, J = 5.2 Hz, 1H, CHO), 4.36 (dq, J = 6.8, 5.2 Hz, 1H,
CHBr), 3.83 (s, 3H, OCH3), 2.16 (s, 3H, O2CCH3), 1.67 (d,
J = 6.8 Hz, 3H, CHBrCH3); 13C NMR (CDCl3, 68 MHz) d 169.7,
159.7, 129.3, 128.6, 113.8, 78.0, 55.3, 50.6, 21.1, 21.1; MS (C.I.) m/z
306, 304 [M+NH4]+; HRMS calcd for [M+NH4]+ C12H19NO3 81Br
306.0528. Found: 306.0527; HRMS calcd for [M+NH4]+
C12H19NO379Br 304.0548. Found: 304.0547.