2338
Y. Kikugawa et al. / Tetrahedron Letters 42 (2001) 2337–2339
triphenylimine (3) via path a and an imino compound,
C19H15ON (4) via path b. Compound 4 was hydrolyzed
to 5, the structure of which was shown to be (4%-
1a (100 mg) and 1d (100 mg) with ZrCl4 (3 mol equiv.)
in benzene (10 ml) and subsequent reduction with Red-
Al (10 mol equiv.) resulted in a mixture of products
(188 mg) after rapid column chromatography. HPLC
analysis7 of the products revealed the exclusive forma-
tion of 6a (85%) and 6d (88%) along with trace
amounts of unidentifiable product (peak area, 1.3%),
the retention time (124.9 min) of which is close to that
of 6c (126.2 min), a crossover compound. On the basis
of the present result, one can conclude that the reaction
proceeds exclusively by an intramolecular mechanism.
1
hydroxybiphenyl-2-yl)phenylmethanone by MS and H
NMR analyses and by comparison of 13C NMR spec-
trum with the related compounds in the literature.6 On
the other hand, in the reaction of 1a with ZrCl4 in
benzene, ZrCl4 coordinates exclusively with the aryloxy
oxygen and assists in the elimination of the aryloxy
group to produce an electron-deficient nitrogen. This
migrated exclusively to the ortho position of the aryloxy
group with no migration to the para position. The
complete absence of the corresponding para-substituted
products can be accounted for by assuming an
intramolecular mechanism proceeding through a tight
ion pair intermediate involving ZrCl4. The formation of
this intermediate presumably prevents the Beckmann
rearrangement and promotes rearrangement of the
imino group to the vicinal ortho position of the aryl
group. Therefore, oxime stereochemistry is not impor-
tant in this rearrangement (Scheme 2).
A typical experimental procedure is as follows: a mix-
ture of 1g (162 mg, 0.71 mmol) and ZrCl4 (828 mg, 3.55
mmol) in benzene (5 ml) was refluxed for 1 h. The
reaction mixture was quenched with 10% HCl (10 ml)
with cooling. The aqueous layer was extracted with
AcOEt (25 ml×2) and the combined organic layer was
washed with brine (30 ml), dried over Na2SO4, and
concentrated. The crude product was determined to be
2-bromophenol (16 mg) by TLC. The aqueous layer
was basified with 10% Na2CO3 (25 ml) and it was
extracted with AcOEt (25 ml×2). The combined organic
layer was washed with brine (30 ml), dried over
Na2SO4, and concentrated. The crude product was
chromatographed on a column of silica gel with hex-
ane–AcOEt (3:1) as an eluent to afford 7g (98.0 mg,
73%), mp 86–87°C (methylcyclohexane). IR (KBr) w:
3400, 3330, 1590, 1490, 1460, 1340, 1230 cm−1. 1H
NMR (CDCl3) l: 3.90 (br s, 2H, NH2), 5.40 (br s, 1H,
OH), 6.62–6.68 (m, 2H, Ar-H), 6.82–6.90 (m, 1H, Ar-
H). MS (EI) m/z (%): 187 (M+, 100), 189 (M++2, 98.1).
Anal. calcd for C6H6BrNO: C, 38.33; H, 3.22; N, 7.45.
Found: C, 38.17; H, 3.13; N, 7.40.
The rearranged products can be reduced without isola-
tion to the corresponding secondary amines with
sodium bis(2-methoxyethoxy)aluminum hydride (Red-
Al) (6a, 77; 6b, 64; 6c, 81; 6d, 78%). Generally they are
partially hydrolyzed to primary amines during work up.
To obtain primary amines, acetoximes are suitable,
because the corresponding rearranged imines are read-
ily hydrolyzed by the usual work-up.
To determine the intramolecular mechanism definitely,
a crossover experiment was performed employing 1a
and 1d. Reaction of almost equimolar concentration of
R4
R4
R4
R3
R5
R6
R3
O
R5
R6
R3
R5
R6
ZrCl4
N
R2
ZrCl4
R2
O
OH
R2
H
R1
H
N
N
R1
R1
1
2
Assumed tight ion pair
H2O
Red-Al
R1
R2
R3 R4 R5
R6
1,2,6,7
R4
R4
a
b
c
d
e
f
g
h
i
j
k
l
n
m
o
C6H5
C6H5
C6H5 4-MeC6H4
C6H5 4-MeC6H4
C6H5
C6H5
H
H
H
H
H
H
Br
H
H
H
H
Me
Cl
Br
Cl
H
H
H
H
H
H
H
CN
H
H
H
H
H
H
H
H
Cl
H
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
CN
H
Br
Cl
R3
R5
R3
R5
R6
R6
OH
R2
OH
C6H5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
HN
6
NH2
H
H
R1
7
Cl
Me
CN
H
Cl
H
Cl
Scheme 2.