Manganese-catalyzed substitution of activated aryl halides (X = Cl, Br and F) and aryl ethers by organomagnesium reagents

Article abstract of DOI:10.1055/s-1999-3644

In the presence of manganese chloride (10%), Grignard reagents readily react in THF with aryl bromides, chlorides and even fluorides, as well as aryl methyl ethers bearing in the ortho- or para-position an electron withdrawing activating group (CN, CH=NR, oxazoline). Aryl and N- or S- alkylmagnesium halides have been used successfully. The reaction is performed under mild conditions (0 °C to room temperature, 30 minutes to 24 hours) and leads to cross-coupling products in good yields.

Full text of DOI:10.1055/s-1999-3644

2138
PAPER
Manganese-Catalyzed Substitution of Activated Aryl Halides (X = Cl, Br and
F) and Aryl Ethers by Organomagnesium Reagents
Gérard Cahiez,* Franck Lepifre, Parfait Ramiandrasoa
Ecole Supérieure de Chimie Organique et Minérale, Département de Chimie (associé au CNRS, EP 1822), 13, boulevard de l'Hautil, F-
95092 Cergy-Pontoise, France
Fax+33(01)30756021
Received 20 June 1999; revised 21 July 1999
lyzed cross-coupling reaction between activated aryl ha-
Abstract: In the presence of manganese chloride (10%), Grignard
lides and Grignard reagents.
reagents readily react in THF with aryl bromides, chlorides and
even fluorides, as well as aryl methyl ethers bearing in the ortho- or
para-position an electron withdrawing activating group (CN,
CH=NR, oxazoline). Aryl and N- or S-alkylmagnesium halides
have been used successfully. The reaction is performed under mild
conditions (0 °C to room temperature, 30 minutes to 24 hours) and
leads to cross-coupling products in good yields.
The preliminary experiments have shown that, in THF,
phenylmagnesium bromide quickly reacts with o-chlo-
robenzonitrile (1a) and the N-phenyl and N-butylimine
1b,c derived from o-chlorobenzaldehyde in the presence
of 10% manganese chloride as catalyst. The reactions
were carried out between 0 to 20 °C and led, within 30
min to 1h, to the corresponding biphenyls 2a-c in good
yields (77-88%, Table 1, entries 1 to 3). The coupling
product 2d was also obtained in excellent yield from the
N-butylimine derived from p-chlorobenzaldehyde (entry
4). On the other hand, the imine 1e derived from m-chlo-
robenzaldehyde did not react under these reaction condi-
tions (entry 5). Other chlorobenzenes substituted in the
ortho-position by an electron-withdrawing group, which
could have a similar activating effect, were also tested.
With ethyl o-chlorobenzoate (1, Fg = COOEt) and with
the N, N-diethylamide of o-chlorobenzoic acid (1, Fg =
CONEt2) the Grignard reagent only reacted with the ester
or the amide group. On the other hand, substitution took
place with the corresponding oxazoline 1f (entry 6) as
well as with (E)-o-chlorostilbene 1g (entry 7). However,
the coupling products 2f, g were obtained respectively in
63% and 56% yield since these two activating groups are
less efficient than a nitrile or an imine. Moreover, the re-
actions are slower (24 h instead of 30 min to 1 h) and re-
quire a large excess of phenylmagnesium bromide (6
equiv.) to go to completion. It is interesting to note that the
use of the (Z)-o-chlorostilbene in place of the (E)-o- chlo-
rostilbene 1g failed. Finally, as expected, when Fg is a
weaker electron-withdrawing group (Entry 8, 1h, Fg = 1-
propenyl), or worse an electron donating group (Entry 9,
1i, Fg = Et2NCH2, but also Fg = MeO, MeOCH2, etc.) the
coupling reaction did not occur.
Key words: manganese, organomagnesium compounds, aryl ha-
lides, aryl ethers, arylation, cross-coupling reaction
The transition-metal-catalyzed cross-coupling reactions
between an organic halide and an organometallic com-
pound are now a classical tool in organic synthesis. Since
the pioneering work of Kharasch, in 1941,1 these reactions
have been extensively studied.2 In recent years the num-
ber of reports has been growing3 since the search for more
efficient and selective C-C bond forming procedures is of
great interest for the elaboration of complex molecules.
On the other hand, reactions having a larger scope of ap-
plication were needed for combinatorial chemistry. Many
transition metals were used, however, the creation of C-
C bonds from alkyl halides is generally performed in the
presence of copper salts,2k,l whereas from aryl and alkenyl
halides (Csp2-X bond) palladium and nickel complexes
are the most common and efficient catalysts.2c-j Unfortu-
nately, for large scale applications palladium and nickel
complexes are expensive and toxic (especially for Ni).
These disadvantages are not only related to the nature of
the metals but also, in some cases, to the nature of the
ligands which are becoming more and more sophisticated.
Thus, the discovery of new environmental friendly proce-
dures is of real current interest. In this field, we have re-
cently described the iron-catalyzed alkenylation of
Grignard reagents, this reaction is very efficient since
even alkenyl chlorides can be successfully used. More-
over, it is performed in the presence of iron acetylaceto-
nate, a non toxic and cheap catalyst.4 The transition-
metal-catalyzed substitution of aryl halides by an organo-
metallic is also a very challenging area of research. This
is especially so for the aryl-aryl coupling which is one of
the best ways to obtain biaryls. This important class of
products is of great interest because of their numerous ap-
plications as polymers, advanced materials (nonlinear op-
tics), liquid crystals, ligands and drugs.5 Now, we would
like to disclose our results about a new manganese-cata-
The reaction described above (Table 1) has been applied
to various chlorobenzenes bearing a nitrile or an oxazoline
moiety as activating group in the ortho-position as well as
an imine in the ortho or para-position (Table 2). It is wor-
thy of note that various aryl but also primary and second-
ary alkylmagnesium compounds were used successfully.
The only attempt to introduce an alkenyl group resulted in
a 32% unoptimized yield of the corresponding styrene 12.
We have also studied the influence of the nature of the
leaving group Z in the case of the imine 19 (Table 3). Sur-
prisingly, the reaction not only occurred when Z = Cl or
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Manganese-Catalyzed Substitution of Activated Aryl Halides
2139
Br but also when Z = F or MeO, and in all cases the cou- The mechanism of the reaction is unclear. However, in
pling product 13 was obtained in excellent yields (90- spite of a few similarities, a nucleophilic aromatic
93%).
substitution6 can be discarded since in this case the fluo-
rine atom would be a better leaving group than bromine or
However, the reaction is clearly slower when Z = F, as
shown by the conversion rates determined after 5 minutes
at 0 °C (Table 4).
Table 2 Manganese-Catalyzed Cross-Coupling Reaction of Grig-
nard Reagents with Activated Aryl Chlorides
Table 1 Mn-Catalyzed Cross-Coupling Reaction between PhMgBr
and Activated Aryl Chlorides 1a-i: Influence of the Nature of the Ac-
tivating Group Fg
ArCl
R
Coupling Product Yield
(Reaction
from RMgX
(%)a
Conditions)
4
Entry Starting Compounds
Coupling
Product 2
(Reaction
Conditions)
Yield of
2 (%)
(0°C, 2 h)
85
60
75
1a–i
5
(0°C, 1 h)
6
(0°C, 1 h)
2a
77a
1
2
(0°C, 30 min)
7
67
(20°C, 2 h)
2b
85a, b,
(0°C, 1 h)
8
64
(20°C, 2 h)
3
4
2c
88a, b
93a, b
9
93b
(0°C, 1 h)
(0°C, 6 h)
2d
(0°C, 6 h)
10
93b
(0°C, 4 h)
11
62b,c
5
6
7
8
9
2e
0
(40°C, 4 h)
(20°C, 24 h)
32b,c
92b
2f
63c
56c
0
12
(40°C, 18 h)
13
(0°C, 30 min.)
14
(20°C, 24 h)
91b
2g
(20°C, 24 h)
(0°C, 30 min.)
15
53b
2h
(20°C, 24 h)
(20°C, 24 h)
16
86b
88b
(20°C, 2 h)
17
(20°C, 2 h)
2i
0
(20°C, 24 h)
18
46b, c
a Yield of isolated product. The reaction was performed with 2 equiv.
of PhMgBr.
(40°C, 24 h)
b Quantitative yields of crude imine 2b–d were obtained. The yield of
isolated product is based respectively on the o-phenylbenzaldehyde
3b (from 2b–c) or the p-phenylbenzaldehyde 3d (from 2d) which
were obtained as the only products after purification by chromatogra-
phy on silica gel.
a
2 equiv. of RMgX were used.
b Isolated yield of the corresponding aldehyde. The purification of the
crude imines 9–18 by chromatography gave the corresponding alde-
hydes 9a–18a (hydrolysis on silica gel) as only products.
c 6 equiv. of RMgX were used.
c Yield of isolated product. The reaction was performed with 6 equiv.
of PhMgBr.
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G. Cahiez et al.
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Table 3 Influence of the Nature of the Leaving Group Z
Scheme 1
Z
Reaction Conditions
Yield (%)a
Br
Cl
F
OMe
0°C, 10 min
0°C, 30 min
0°C, 2 h
92
93
90
91
20°C, 20 min
only the manganese-catalyzed reaction occurred (entries 5
and 6).
a Isolated yield of aldehyde 13a. In all cases, the purification of the
crude imine 13 by chromatography gave as the only product the cor-
responding aldehyde 13a (hydrolysis on silica gel). 2 equivalents of
BuMgCl were used.
A mechanism similar to those established for palladium-
or nickel-catalyzed aryl-aryl coupling reactions can be
involved.5 Such reactions are well-known with aryl bro-
mides, and iodides, and to a lesser extent chlorides.5 How-
ever, only a few examples are reported with aryl methyl
chlorine7 contrary to our observations (Table 4). In addi-
tion, in the presence of manganese chloride both ortho-
and para-activated aryl chlorides reacted (Table 2, com-
pounds 9-14 and 15-18 respectively) whereas in the ab-
sence of catalyst only the substitution of ortho-activated
aryl halides has been described.6 Finally, under the condi-
tions described by Meyers for the nucleophilic aromatic
substitution of o-methoxy phenyloxazoline by butylmag-
nesium bromide (85%),8 the o-chlorophenyloxazoline 1f
did not react. On the contrary, in the presence of 10%
MnCl2 the coupling product 7 was obtained in 67% yield
(Scheme 1).
Table 5 Nucleophilic Aromatic Substitution Versus Manganese-
Catalyzed Substitution of o-Chloro-, o-Fluoro and o-
Methoxyben1zaldimines 19 by Grignard Reagents
Entry ArZ
RMgX
Reaction
Yields of
Product
(%)
Conditions
In fact, the manganese-catalyzed procedure compares fa-
vorably to the aromatic nucleophilic substitution reaction
whatever the nature of the leaving group (Table 5). Thus,
from N-butylbenzaldimines 19 the substitution took place
under the Meyers conditions8 when Z = MeO (entry 2) but
in the presence of manganese chloride (entry 1) the reac-
tion was faster (20 min instead of 24 h) and led to a better
yield (91% instead of 75%). When Z = F, the beneficial
influence of manganese chloride is still more obvious
(90% instead of 40%, entries 3 and 4) and when Z = Cl
1
20°C, 20 min 91a
10% MnCl2
BuMgCl
2
3
20°C, 24 h
75b
90a
0°C, 2 h,
10% MnCl2
BuMgCl
4
5
20°C, 24 h
40b
88a
Table 4 Influence of the Nature of the Leaving Group Z on the Re-
action Rate
20°C, 2 h,
10% MnCl2
C6H5MgBr
6
20°C, 24 h
0b
a Quantitative yields of crude imine 2b (entries 1-4) and 13 (entries
5,6) were obtained. The yield of isolated product is based respective-
ly on the corresponding aldehyde 3b (from 2b) or 13a (from 13) ob-
tained after chromatography on silica gel.
Z
Br
98
Cl
78
F
Conversion rate (%)a
after 5 min at 0°C
30
b Yield determined by GC.
a Determined by GC analysis of the crude reaction mixture after hy-
drolysis. Only starting material and imine 13 were detected.
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Manganese-Catalyzed Substitution of Activated Aryl Halides
2141
fluorides. Of course, as far as the insertion of a low valent In conclusion, we have reported above a new general pro-
metal into a C-X bond is concerned, manganese cannot cedure for the manganese-catalyzed substitution of acti-
be compared to palladium and nickel and it is difficult to vated aryl halides (X = Cl, Br, F) and aryl methyl ethers
conclude.
by organomagnesium reagents. The electron-withdrawing
activating group can be located in the ortho-position (CN,
CH=NR or oxazoline) as well as in the para-position (CH
= NR) of the leaving group. For large-scale applications
this reaction is environmental friendly and takes place un-
der mild conditions (0 °C to room temperature) to give
good to excellent yields of cross-coupling products. Final-
ly, It should be noted that the catalyst, MnCl2, is a cheap
material.
When two different leaving groups (for instance F and Cl)
are present at the ortho-position of the activating function-
al group, it is possible to obtain directly the disubstituted
product. Thus, the o-chloro-o’-fluorobenzaldimine 20 was
easily converted to the o,o’-dialkylated compound 21 ac-
cording to a one-pot procedure (Scheme 2).
THF was distilled from sodium benzophenone ketyl under a N2 at-
mosphere before use. All products were isolated by chromatogra-
phy on silica gel. GC analyses were performed on a Fisons GC
8000, capillary column SGE 25QC5/BP1 (25 m x 0.53 mm, 0.5 mm
film thickness). 1H and 13C NMR spectra (CDCl3, d ppm, 1H ±0.01,
13C ±0.05, internal standard TMS, J values in Hz ± 0.3) were record-
Scheme 2
1
ed on a JEOL JNM-EX 270 (270 MHz for H) spectrometer. IR
spectra (cm-1) were recorded on a FT spectrometer, Nicolet Impact
400 (OMNIC software). All new compounds gave satisfactory mi-
croanalyses: C± 0.24, H±0.29 except for the aldehydes 12a, 13a,
14a, 16a, 17a and 21a, which were not stable enough at r.t. These
compounds have been only characterized according to their IR and
NMR spectra.
However, by combining the nucleophilic aromatic substi-
tution and the manganese-catalyzed procedure described
above, it is possible to substitute selectively the fluorine
atom, and then, in the presence of 10% manganese chlo-
ride, the chlorine atom according to a two-step procedure
(Table 6).
(2-Butylbenzylidene)butylamine (13) and 2-Butylbenzaldehyde
(13a); General Procedure
To a solution of (2-chlorobenzylidene)butylamine (1c) (392 mg, 2
mmol) in THF (5 mL) was added MnCl2 (26 mg, 0.2 mmol). A so-
lution of butylmagnesium chloride (4 mmol, 1.2 M in THF) was
then added dropwise between 0 and 5 °C. After stirring for 30 min,
the reaction mixture was hydrolyzed at 0 °C with saturated aqueous
NH4Cl (10 mL). After extraction with Et2O (2 x 30 mL), the com-
bined organic layers were washed with brine, dried (MgSO4), and
concentrated under reduced pressure to give 444 mg of crude imine
13 (98% yield). This crude material was purified by chromatogra-
phy on silica gel (CH2Cl2:pentane, 70:30) to give 298 mg of alde-
hyde 13a (92%) as an oil.
Table 6 Two-steps Selective Substitution of N-butyl-o-chloro-o’-
fluorobenzaldimine 19
N-(2-Butylbenzylidene)butylamine (13)
IR (neat): n = 3065, 3025, 1640, 1600, 1295, 976, 758 cm-1.
1H NMR (CDCl3): d = 0.92 (t, 3 H, J = 7.0 Hz), 0.95 (t, 3H, J = 7.0
Hz), 1.30-1.46 (m, 4H), 1.50-1.61 (m, 2H), 1.64-1.75 (m, 2H),
2.77-2.83 (m, 2H), 3.62 (dt, 2H, J = 1.0, 6.9 Hz), 7.12-7.30 (m,
3H), 7.88 (dd, 1H, J = 1.7, 7.6 Hz), 8.57 (s, 1H).
13C NMR (CDCl3): d = 13.73, 13.78, 20.29, 22.37, 32.22, 32.89,
34.11, 61.74, 126.00, 127.30, 129.81, 133.75, 142.10, 158.83.
2-Butylbenzaldehyde (13a).
Entry
R1
R2
Product
Yield a
(% )
IR (neat): n = 2965, 1699, 1600, 1573, 758 cm-1.
1H NMR (CDCl3): d = 0.93 (t, 3H, J = 7.3 Hz), 1.33-1.46(m, 2H),
1.53-1.64 (m, 2H), 2.98-3.04 (m, 2H), 7.23-7.35 (m, 2H), 7.44-
7.50 (m, 1H), 7.81 (dd, 1H, J = 1.0, 7.6 Hz), 10.27 (s, 1H).
13C NMR (CDCl3): d = 13.75, 22.43, 32.02, 34.38, 126.18, 130.78,
131.18, 133.46, 133.55, 145.59, 192.04.
1
2
3
4
Bu
C6H5
Bu
–
–
22a
23a
24a
25a
90b
83c
C6H5
p-
MeOC6H5
83d,e
75c,e
C6H5
Biphenyl-2-carbonitrile (2a)
a Crude imines 22–25 were isolated as the corresponding aldehydes
IR (neat): n = 3061, 2229, 1598, 1483, 759, 737, 694 cm-1.
22a–25a by chromatography on silica gel.
1H NMR (CDCl3): d = 7.4-7.7 (m, 8H), 7.77 (dd, 1H, J = 1.0, 8.0
Hz).
13C NMR (CDCl3): d = 110.95, 118.55, 127.40, 128.55, 129.90,
132.70, 133.55. 137.90, 145.2.
b 0°C, 1 h.
c 20°C, 5 h.
d 20°C, 2 h.
e Yield based on the crude imine 22 or 23 used as starting material.
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2142
G. Cahiez et al.
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Biphenyl-2-carboxaldehyde (3b)
2-(2-Cyclohexylphenyl)-4,4-dimethyl-2-oxazoline (8)
IR (neat): n = 1695, 1597, 1474, 1253, 1196, 758, 747, 703 cm-1.
IR (neat): n = 2965, 2925, 2853, 1653, 1450, 1308, 1036, 751 cm-1.
1H NMR (CDCl3): d = 7,32-7,50 (m, 7H), 7,61 (dt, 1H, J = 1.3, 7.6
1H NMR (CDCl3): d = 1.21-1.46 (m, 11H), 1.69-1.89 (m, 5H),
3.20-3.30 (m, 1H), 4.08 (s, 2H), 7.15-7.21 (m, 1H), 7.30-7.40 (m,
2H), 7.56 (dd, 1H, J = 1.3, 7.6 Hz).
13C NMR (CDCl3): d = 26.08, 26.87, 28.14, 33.96, 40.09, 67.66,
78.58, 125.10, 125.86, 127.49, 129.43, 130.15, 147.26, 162.86.
Hz), 8.01(dd, 1H, J = 1.3, 7.9 Hz), 9.97 (d, 1H, J = 1.0 Hz).
13C NMR (CDCl3): d = 127.38, 127.62, 127.96, 128.27, 129.95,
130.62, 133.40, 133.53, 137.56, 145.77, 192.22.
Biphenyl-4-carboxaldehyde (3d)
mp: 57-58 °C (commercial product: 57-59 °C).
IR (nujol): n = 1699, 1600, 1220, 1175, 837, 771 cm-1.
1H NMR (CDCl3): d = 7.36-7.49 (m, 3H), 7.58-7.62 (m, 2H),
7.70-7.73 (m, 2H), 7.90-7.93 (m, 2H), 10.02 (s, 1H).
13C NMR (CDCl3): d = 127.69, 127.98, 128.82, 129.36, 130.60,
135.49, 139.98, 147.46, 192.25.
4’-Methoxybiphenyl-2-carboxaldehyde (9a)
mp: 52-53 °C (Lit.11: 52-53 °C).
IR (nujol): n = 1693, 1600, 1513, 1248, 1188, 1035, 850, 770 cm-1.
1H NMR (CDCl3): d = 3.87 (s, 3H), 6.98-7.03 (m, 2H), 7.26-7.34
(m, 2H), 7.42-7.49 (m, 2H), 7.59-7.65 (m, 1H), 7.99-8.02 (m,
1H), 10.0 (s, 1H).
13C NMR (CDCl3): d = 55.34, 113.91, 127.33, 127.56, 129.96,
130.76, 131.28, 133.51, 133.71, 145.60, 159.67, 192.59.
2-(2-Biphenyl)-4,4-dimethyl-2-oxazoline (2f)
IR (neat): n = 3058, 3032, 2965, 2932, 2893, 1659, 1310, 1069,
1036, 751, 705 cm-1.
2-(1-Naphthalenyl)benzaldehyde (10a)
mp: 80-82 °C.
1H NMR (CDCl3): d = 1.29 (s, 6H), 3.79 (s, 2H), 7.31-7.42 (m, 7H),
7.44-7.49 (m, 1H), 7.71-7.75 (m, 1H).
IR (neat): n = 2754, 1699, 1600, 1394, 1261, 1195, 811, 791 cm-1.
13C NMR (CDCl3): d = 27.84, 67.28, 79.25, 126.86, 127.01, 127.80,
128.09, 128.18, 129.90, 129.94, 130.24, 140.95, 141.47, 163.59.
1H NMR (CDCl3): d = 7,38-7.61 (m, 7H), 7.67-7.73 (m, 1H),
7.92-7.95 (m, 2H), 8.10-8.13 (m, 1H), 9.63 (d, 1H, J = 0.7 Hz).
2-(2-Phenylethenyl)biphenyl (2g)
IR (neat): n = 3056, 3024, 1598, 1493, 1474, 1450, 1435, 964, 746,
702 cm-1.
13C NMR (CDCl3): d = 124.97, 125.69, 126.14, 126.72, 127.02,
128.12, 128.32, 128.59, 131.64, 132.63, 133.31, 133.58, 134.73,
135.34, 144.15, 191.91.
1H NMR (CDCl3): d = 6.97-7.04 (m, 1H), 7.07-7.39 (m, 14H),
7.70-7.75 (m, 1H).
13C NMR (CDCl3): d = 125.80, 126.50, 127.06, 127.42, 127.49,
127.53, 127.75, 128.09, 128.57, 129.40, 129.86, 130.26, 135.33,
137.52, 140.83, 141.08.
2’-Methylbiphenyl-2-carboxaldehyde (11a)
IR (neat): n = 3065, 3018, 2925, 2839, 2747, 1699, 1600, 1474,
1447, 1255, 1202, 764 cm-1.
1H NMR (CDCl3): d = 2.09 (s, 3H), 7.16-7.35 (m, 5H), 7.44-7.51
(m, 1H), 7.59-7.65 (m, 1H), 8.02 (dd, 1H, J = 1.3, 7.6 Hz), 9.75 (d,
1H, J = 0.7 Hz).
13C NMR (CDCl3): d = 20.22, 125.57, 126.95, 127.71, 128.18,
129.97, 130.08, 130.64, 133.62, 133.69, 136.03, 137.36, 145.53,
192.09.
4’-Methoxybiphenyl-2-carbonitrile (4)
mp: 84-85 °C (Lit.10:81-82 °C).
IR (neat): n = 2218, 1612, 1246, 1181, 1040, 837, 750 cm-1.
1H NMR (CDCl3): d = 3.87 (s, 3H), 7.0-7.05 (m, 2H), 7.40 (dt, 1H,
J = 1.3, 7.6 Hz), 7.47-7.54 (m, 3H), 7.62 (dt, 1H, J = 1.3, 7.6 Hz),
7.73-7.76 (m, 1H).
2-(2-Methylpropenyl)benzaldehyde (12a)
IR (neat): n = 2985, 2939, 2912, 2859, 1700, 1600, 1454, 1222,
1202, 824, 760 cm-1.
1H NMR (CDCl3): d = 1.66 (d, 3H, J = 1.0 Hz), 1.96 (d, 3H, J = 1.3
Hz), 6.58 (s, 1H), 7.23 (d, 1H, J = 7.9 Hz), 7.33-7.38 (m, 1H),
7.51-7.57 (m, 1H), 7.87-7.90 (m, 1H), 10.22 (s, 1H).
13C NMR (CDCl3): d = 55.35, 111.0, 114.16, 118.98, 127.03,
129.86, 129.97, 130.48, 132.76, 133.73, 145.17, 160.02.
2-Butylbenzonitrile (5)
IR (neat): n = 2958, 2931, 2863, 2224, 1485, 1449, 762 cm-1.
13C NMR (CDCl3): d = 19.37, 26.02, 121.24, 126.79, 128.03,
130.76, 133.53, 133.76, 139.19, 142.15, 192.63.
1H NMR (CDCl3): d = 0.95 (t, 3H, J = 7.3 Hz), 1.39 (sext, 2H, J =
7.3 Hz), 1.60-1.71 (m, 2H), 2.80-2.86 (m, 2H), 7.23-7.33 (m, 2H),
7.50 (dt, 1H, J = 1.3, 7.8 Hz), 7.58 (dd, 1H, J = 1.3, 7.8 Hz).
13C NMR (CDCl3): d = 13.70, 22.19, 32.90, 34.16, 112.13, 118.04,
126.16, 129.36, 132.54, 146.65.
(2-Cyclohexylbenzylidene)butylamine (14)
1H NMR (CDCl3): d = 0.96 (t, 3H, J = 7.3 Hz), 1.12-1.56 (m, 6H),
1.65-1.88 (m, 8H), 3.01-3.08 (m, 1H), 3.64 (dt, 2H, J = 1.0, 6.9
Hz), 7.18-7.36 (m, 3H), 7.85 (dd, 1H, J = 1.3, 7.9 Hz), 8.66 (s, 1H).
2-Cyclohexylbenzonitrile (6)
N-2-Cyclohexylbenzaldehyde (14a)
IR (neat): n = 2932, 2853, 2223, 1600, 1480, 1447, 764 cm-1.
IR (neat): n = 2925, 2859, 1700, 1600, 1454, 1215, 758 cm-1.
1H NMR (CDCl3): d = 1.18-1.56 (m, 5H), 1.75-1.95 (m, 5H),
2.92-3.03 (m, 1H), 7.23-7.29 (m, 1H), 7.50-7.60 (m, 2H).
13C NMR (CDCl3): d = 25.73, 26.42, 33.48, 42.55, 111.61, 118.08,
126.11, 126.36, 132.70, 132.74, 151.27.
1H NMR (CDCl3): d = 1.20-1.95 (m, 10H), 3.45-3.65 (m, 1H),
7.31-7.37 (m, 1H), 7.43 (d, 1H, J = 7.9 Hz), 7.51-7.57 (m, 1H),
7.82 (d, 1H, J = 7.6 Hz), 10.38 (s, 1H).
13C NMR (CDCl3): d = 26.13, 26.86, 34.41, 38.22, 126.03, 126.61,
131.35, 133.08, 133.91, 150.44, 192.13.
2-(2-Butylphenyl)-4,4-dimethyl-2-oxazoline (7)
IR (neat): n = 2975, 2932, 1659, 1467, 1308, 1195, 1036 cm-1.
4’-Methoxybiphenyl-4-carboxaldehyde (15a)
mp: 105-107 C (Lit.12: 104-106 °C).
IR (neat): n = 1680, 1600, 1301, 1182, 1036, 824 cm-1.
1H NMR (CDCl3): d = 3.84 (s, 3H), 6.96-7.02(m, 2H), 7.54-7.60
(m, 2H), 7.66-7.70 (m, 2H), 7.87-7.92 (m, 2H), 10.01 (s, 1H).
1H NMR (CDCl3): d = 0.94 (t, 3H, J = 7.3 Hz), 1.29-1.42 (m, 8H),
1.49-1.60 (m, 2H), 2.90-2.96 (m, 2H), 4.03-4.09 (m, 2H), 7.16-
7.26 (m, 2H), 7.33 (t, 1H, J = 7.6 Hz), 7.67 (d, 1H, J = 7.6 Hz).
13C NMR (CDCl3): d = 13.77, 22.50, 28.14, 33.60, 33.66, 67.51,
78.42, 125.26, 127.30, 129.72, 130.03, 130.08, 142.96, 162.57.
13C NMR (CDCl3): d = 55.26, 114.36, 126.90, 128.37, 130.19,
131.88, 134.54, 146.61, 160.0, 191.77.
Synthesis 1999, No. 12, 2138–2144 ISSN 0039-7881 © Thieme Stuttgart · New York

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Manganese-Catalyzed Substitution of Activated Aryl Halides
2143
N-(4-Butylbenzylidene)butylamine (16)
13C NMR (CDCl3): d = 13.78, 13.86, 20.40, 22.59, 32.85, 33.06,
33.55, 62.07, 126.92, 128.64, 129.38, 133.19, 134.30, 144.29,
158.78.
1H NMR (CDCl3): d = 0.92 (t, 3H, J = 7.3 Hz), 0.94 (t, 3H, J = 7.3
Hz), 1.25-1.45 (m, 4H), 1.55-1.73 (m, 4H), 2.60-2.66 (m, 2H),
3.59 (t, 2H, J = 6.6 Hz), 7.21 (d, 2H, J = 7.9 Hz), 7.63 (d, 2H, J =
7.9 Hz), 8.24 (s, 1H).
2-Butyl-6-chlorobenzaldehyde (22a)
IR (neat): n = 2959, 2932, 1699, 1593, 1189, 791 cm-1.
13C NMR (CDCl3): d = 13.82, 20.36, 22.21, 32.96, 33.37, 35.49,
61.38, 127.89, 128.55, 133.85, 145.53, 160.54.
1H NMR (CDCl3): d = 0.93 (t, 3H, J = 7.3 Hz), 1.25-1.45 (m, 2H),
1.47-1.58 (m, 2H), 2.85-2.95 (m, 2H), 7.14-7.17 (m, 1H), 7.25-
7.38 (m, 2H), 10.60 (s, 1H).
4-Butylbenzaldehyde (16a)
IR (neat): n = 2957, 2931, 2859, 2733, 1703, 1606, 1576, 1306,
13C NMR (CDCl3): d = 13.78, 22.59, 33.23, 33.59, 128.12, 129.81,
1213, 1168, 824 cm-1.
130.53, 133.31, 138.56, 147.12, 192.09.
1H NMR (CDCl3): d = 0.93 (t, 3H, J = 7.3 Hz), 1.26-1.42 (m, 2H),
1.56-1.67 (m, 2H), 2.64-2.70 (m, 2H), 7.32 (d, 2H, J = 8.2 Hz),
7.78 (d, 2H, J = 8.2 Hz), 9.95 (s, 1H).
13C NMR (CDCl3): d = 13.73, 22.16, 33.03, 35.71, 128.89, 129.68,
134.21, 150.24, 191.79.
3-Chlorobiphenyl-2-carboxaldehyde (23a)
mp: 57-58 °C.
IR (nujol): n = 1699, 1586, 1208, 764, 705 cm-1.
1H NMR (CDCl3): d = 7.25-7.36 (m, 3H), 7.38-7.51 (m, 5H),
10.04 (s, 1H).
13C NMR (CDCl3): d = 128.09, 128.23, 129.38, 129.94, 131.61,
132.51, 134.16, 137.65, 146.29, 190.80.
N-(4-Cyclohexylbenzylidene)butylamine (17)
1H NMR (CDCl3): d = 0.94 (t, 3H, J = 7.3 Hz), 1.23-1.50 (m, 7H),
1.52-1.86 (m, 7H), 2.40-2.70 (m, 1H), 3.60 (t, 2H, J = 6.5 Hz),
7.25 (d, 2H, J = 8.1 Hz), 7.65 (d, 2H, J = 8.1 Hz), 8.23 (s, 1H).
3-Butylbiphenyl-2-carboxaldehyde (24a)
IR (neat): n = 2959, 2939, 1693, 1593, 1190, 771, 705 cm-1.
13C NMR (CDCl3): d = 13.75, 20.29, 25.95, 26.65, 32.90, 34.13,
44.40, 61.31, 126.88, 127.91, 133.94, 150.55, 160.47.
1H NMR (CDCl3): d = 0.95 (t, 3H, J = 7.3 Hz), 1.44 (sext, 2H, J =
7.3 Hz), 1.56-1.68 (m, 2H), 2.97-3.03 (m, 2H), 7.21-7.46 (m, 8H),
9.94 (s, 1H).
13C NMR (CDCl3): d = 13.91, 22.73, 33.55, 34.04, 127.71, 128.14,
128.41, 129.90, 130.17, 131.90, 132.33, 138.96, 144.64, 146.83,
194.18.
4-Cyclohexylbenzaldehyde (17a)
IR (neat): n = 2926, 2659, 2720, 1706, 1613, 1447, 1308, 1215,
1175, 824 cm-1.
1H NMR (CDCl3): d = 1.22-1.50 (m, 5H), 1.73-2.05 (m, 5H),
2.52-3.00 (m, 1H), 7.34 (d, 2H, J = 8.1 Hz), 7.78 (d, 2H, J = 8.1
Hz), 9.94 (s, 1H).
13C NMR (CDCl3): d = 25.77, 26.45, 33.82, 44.66, 127.30, 129.70,
134.32, 155.08, 191.68.
4’-Methoxy-3-phenylbiphenyl-2-carboxaldehyde (25a)
mp: 86-87 °C.
IR (nujol): n = 1700, 1613, 1580, 1262, 1175, 844, 811, 764 cm-1.
1H NMR (CDCl3): d = 3.81 (s, 3H), 6.92-6.97(m, 2H), 7.24-7.43
(m, 9H), 7.53 (t, 1H, J = 7.6 Hz), 9.94 (s, 1H).
2’-Methylbiphenyl-4-carboxaldehyde (18a)
mp: 55-56 °C.
IR (nujol): n = 1699, 1606, 1209, 1169, 844, 765 cm-1.
1H NMR (CDCl3): d = 2.26 (s, 3H), 7.18-7.32 (m, 4H), 7.42-7.50
(m, 2H), 7.89-7.93 (m, 2H), 10.03 (s, 1H).
13C NMR (CDCl3): d = 55.13, 113.55, 127.42, 127.98, 129.92,
130.26, 130.73, 131.36, 131.54, 133.05, 139.68, 143.86, 143.97,
159.17, 193.60.
13C NMR (CDCl3): d = 20.24, 125.86, 127.92, 129.33, 129.43,
129.76, 130.46, 134.77, 134.93, 140.39, 148.19, 191.80.
Acknowledgement
N-(2,6-Dibutylbenzylidene)butylamine (21)
We thank the CNRS and the Ecole Supérieure de Chimie Orga-
nique et Minérale (ESCOM) for their financial support.
IR (neat): n = 2956, 2929, 2871, 2859, 1647, 1463, 1378, 750 cm-1.
1H NMR (CDCl3): d = 0.90 (t, 6H, J = 7.3 Hz), 0.97 (t, 3H, J = 7.3
Hz), 1.25-1.57 (m, 10H), 1.71 (quint, 2H, J = 6.9 Hz), 2.66-2.72
(m, 4H), 3.64 (dt, 2H, J = 1.0, 6.9 Hz), 6.97-7.08 (m, 2H), 7.13-
7.19 (m, 1H), 8.60 (s, 1H).
13C NMR (CDCl3): d = 13.77, 13.84, 20.49, 22.61, 32.96, 33.07,
33.51, 62.19, 127.19, 128.28, 134.18, 141.53, 160.56.
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2,6-Dibutylbenzaldehyde (21a)
IR (neat): n = 2957, 2931, 2872, 2860, 2767, 1694, 1592, 1463,
1184 cm-1.
1H NMR (CDCl3): d = 0.93 (t, 6H, J = 7.3 Hz), 1.39 (quint, 4H, J =
7.3 Hz), 1.51-1.62 (m, 4H), 2.89-2.95 (m, 4H), 7.08 (d, 2H, J = 7.6
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Article Identifier:
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Synthesis 1999, No. 12, 2138–2144 ISSN 0039-7881 © Thieme Stuttgart · New York