Copper-catalyzed oxybromination and oxychlorination of primary aromatic amines using LiBr or LiCl and molecular oxygen

Article abstract of DOI:10.1002/adsc.200800223

Nuclear oxybromination of unprotected aromatic primary amines catalyzed by copper(II) acetate [Cu(OAc)₂] under mild conditions has been developed, in which bromide ions are used as halogenating agents and dioxygen as a final oxidant. The catalyst shows not only high regioselectivity for para- or ortho-isomers but also a remarkable chemoselectivity for monobromination. Oxychlorination of aniline can also be performed under similar conditions, albeit with lower selectivities, with N-phenylacetamide being the main by-product. This simple catalytic method represents ecologically benign and economically attractive synthetic pathway to expensive low-volume aromatic haloamines.

Full text of DOI:10.1002/adsc.200800223

FULL PAPERS
DOI: 10.1002/adsc.200800223
Copper-Catalyzed Oxybromination and Oxychlorination of
Primary Aromatic Amines Using LiBr or LiCl and Molecular
Oxygen
Luciano Menini,a Joyce C. da Cruz Santos,a and Elena V. Gusevskayaa,*
a
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil
Fax : (+55)-31-3409-5700; e-mail: elena@ufmg.br
Received: April 11, 2008; Revised: June 17, 2008; Published online: August 19, 2008
Abstract: Nuclear oxybromination of unprotected ar- with lower selectivities, with N-phenylacetamide
omatic primary amines catalyzed by copper(II) ace- being the main by-product. This simple catalytic
tate [Cu(OAc)2] under mild conditions has been de- method represents ecologically benign and economi-
G
veloped, in which bromide ions are used as halogen- cally attractive synthetic pathway to expensive low-
ating agents and dioxygen as a final oxidant. The cat- volume aromatic haloamines.
alyst shows not only high regioselectivity for para- or
ortho-isomers but also a remarkable chemoselectivity
for monobromination. Oxychlorination of aniline can Keywords: amines; copper; oxybromination; oxy-
also be performed under similar conditions, albeit chlorination; oxygen
Introduction
still remains a big challenge to leave intact carbon-
chlorine bonds and selectively reduce a nitro group in
Halogenation of aromatic compounds is a fundamen- the same molecule.[2,5,21]
tal reaction of organic chemistry widely involved in
In oxidative halogenation, halide ions can be used
the manufacture of many bulk and fine chemicals.[1,2,3] as a halogen source together with a suitable oxidant;
Bromoaromatics are particularly versatile synthetic thus, this method represents more ecologically benign
starting materials due to the possibility of their use in and economically attractive pathway to haloaromatics
carbon-carbon bond formation reactions via Heck, than classical electrophilic substitutions. Main advan-
Stille and Suzuki transmetallation processes.[4] Aro- tages of oxyhalogenation, which make it safer and
matic haloamines are used for the manufacture of greener, are the use of low value and easy to handle
polyurethanes, rubber chemicals, agricultural products metal halides as halogenating agents and atom econo-
and drugs.[5,6]
my, i.e., a full utilization of halogen atoms instead of
Historically, primary amines, due to their high reac- using only half of the available amount. Most of the
tivity, were converted to the corresponding anilides if reported examples of oxybromination of anilines in-
monohalogenated products were desired in conven- volve hydrogen peroxide or peroxo compounds as ox-
tional electrophilic aromatic substitutions.[7] However, idants[12–19] and only few works use the most attractive
in recent years, several methods have been developed oxidant – molecular oxygen.[20,22]
allowing one to control polybromination of unprotect-
ed anilines and obtain monosubstituted derivatives in
In spite of the obvious advantages, little was
achieved on the aerobic oxyhalogenation of aromatics
AHCTREUNG
high yields.[8–19] Some of these methods involve elec- in general.[20,22–25] Only few examples of the use of
trophilic bromination of aromatic rings but use bromi- bromide or chloride salts as a halogen source have ap-
nating agents other than molecular bromine, such as peared, all reporting low substrate conversions and/or
N-bromosuccinimide,[8,9] a hexamethylenetetramine- low selectivities for individual products, although high
bromine complex,[10] and an alkyl bromide/sodium hy- dioxygen pressures have been applied (20–70
dride/DMSO combination;[11] whereas the others are atm).[22–24] Under atmospheric pressure, high yields of
based on oxidative bromination.[12–20] As far as chloro- monobrominated aromatics were achieved with hy-
anilines are concerned, they are usually produced by drobromic acid, from which molecular bromine was
the hydrogenation of corresponding chloronitroben- generated in situ using sodium nitrite[25] or a P-Mo-V
zenes; however, this process is heavily complicated by heteropoly acid[20] as catalyst. Recently, oxychlorina-
a concomitant hydrodechlorination reaction so that it tion and oxybromination of phenylpyridines giving
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Copper-Catalyzed Oxybromination and Oxychlorination
FULL PAPERS
mono- and dihalogenated products under one atmos-
phere of dioxygen have been reported; however, the
method involves the use of X2CHCHX2 (X=Cl, Br)
as a halogen source and Cu(OAc)2 as the catalyst in
A
the case of oxychlorination and as a stoichiometric re-
agent in the case of oxybromination.[26] In the only
work found in the literature which describes oxy-
chlorination and oxybromination of aniline with di-
oxygen, tert-butyl hydroperoxide was added as initia-
tor.[22] Nevertheless, the process resulted in complex
mixtures of isomeric mono-, di-, and trihalogenated
products and in low substrate conversions even at ca.
30 atm of dioxygen (ca. 10% in 10 h).
In previous works, we have reported a remarkable
activity of copper (II) salts to catalyze aerobic oxida-
tive monochlorination and monobromination of
phenol and activated phenolic compounds with lithi-
um chloride or bromide under atmospheric pressure,
which allows us to avoid the use of hazardous re-
agents, such as hydrobromic acid and molecular chlor-
ine and bromine.[27–29] However, we observed that
non-phenolic compounds were not reactive in these
reactions; moreover, phenols having electron-with-
drawing substituents also did not react at all. A sug-
gested explanation was a necessary formation of
Cu(II) (phenolate) complexes as key intermediates, in
which a rate-determining one-electron oxidation of
phenolate by Cu(II) to the corresponding phenoxy
radicals took place. It was, therefore, surprising for us
to find latter that aniline and even deactivated ani-
lines readily undergo nuclear bromination under simi-
lar conditions.
In the present paper, we report for the first time a
simple and highly selective Cu-catalyzed oxidative
monobromination of unprotected aromatic amines
under mild aerobic conditions, using lithium bromide
as a halogen source and molecular oxygen as a final
oxidant. Oxychlorination of these substrates was also
investigated; however, it resulted in much more
modest selectivities because of the concomitant N-
acetoxylation of the substrate.
Scheme 1. Structures of aromatic amines and corresponding
products.
Results and Discussion
Oxybromination
We have found that solutions of aniline (1a) in acetic
acid containing LiBr and catalytic amounts of Cu-
(OAc)2 readily consume dioxygen in stoichiometric
proportions. The formation of several products has
been observed, with their composition being strongly
dependent on the reaction time and applied condi-
tions. Two major products were identified as ortho-
and para-bromoanilines, 1b and 1c; and the main
minor products as dibrominated aniline 1e and N-
Figure 1. Oxybromination of aniline (1a) in acetic acid cata-
lyzed by Cu
(OAc)2]=0.05M; [LiBr]=0.8M; 808C; O2 (1 atm). 1b: 2-
bromoaniline; 1c: 4-bromoaniline; 1e: 2,4-dibromoaniline;
A
AHCTREUNG
phenylacetamide (6) (Scheme 1). Figure 1 shows the 6: N-phenylacetamide.
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Luciano Menini et al.
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Table 1. Copper-catalyzed oxybromination of aromatic amines with dioxygen.[a]
Run Substrate
Time [h] Conversion [%]
Selectivity [%]
ortho- (1b–4b) para- (1c) dibromo (1e or 2e) Smono
[b]
1
aniline (1a)
aniline (1a)
4
5
7
4
90
57
90
100
65
90
92
90
100
100
6
15
16
13
16
100
86
86
55
84
72
80
–
–
–
–
–
7
–
15
4
–
10
14
8
–
–
70
100
85
96
100
86
86
85
100
100
–
2[c]
3[d]
4
aniline (1a)
4-butylaniline (2a)
1
2.5
3.5
3.5
5[c]
6[d]
7
4-butylaniline (2a)
4-butylaniline (2a)
ethyl 4-aminobenzoate (3a) 4.5
4-aminobenzonitrile (4a)
N-methylaniline (5a)
85
100
100
–
8
20
10
6
–
–
–
9
–
–
10[e] ethyl 4-aminobenzoate (3a)
60
100
100
[a]
Conditions: solvent – acetic acid, [substrate]=0.40M; [Cu(OAc)2]=0.05M; [LiBr]=0.80M; 808C; O2 (1 atm). Conver-
A
sion and selectivity were determined by GC. Product and substrate structures are given in Scheme 1.
Selectivity for monobrominated products.
608C.
[b]
[c]
[d]
[e]
[aniline]=0.20M; [Cu
A
Air was bubbled through the reaction solution.
progress of the reaction presented in Table 1, run 1. as all the substrate is nearly consumed to avoid fur-
Up to ca. 70% conversion, monobrominated anilines ther transformations of the monobrominated prod-
1b and 1c are exclusively formed; with para-isomer 1c ucts.
accounting for ca. 80% of the mass balance; then,
The reaction of aniline with bromide ions and mo-
their concentrations start to decline and dibromoani- lecular oxygen, i.e., oxidative bromination, formally
line 1e along with several unidentified products consists in a nucleophilic substitution of the aromatic
(probably, polybromoanilines) appear in the reaction hydrogen by BrÀ, oxidation of HÀ by Cu(II) and reox-
solutions. At 90% conversion, the selectivity for mon- idation of the reduced Cu(I) species by dioxygen
obromination drops to 70% and at a complete conver- (Scheme 2). The process does not involve a genera-
sion to 42%.
tion of molecular bromine in situ as the reaction be-
By varying the reaction conditions, we have man- tween Cu(II) and BrÀ is thermodynamically unfavora-
aged to control the di- and polybromination of aniline ble; as a result, di- and polybromination of unprotect-
and obtained excellent results in terms of both activi- ed aniline can be avoided in our system, differently
ty and selectivity. At 608C, selectivity as high as 85% from what usually occurs in conventional electrophilic
for monobromination has been maintained until 90% aromatic substitutions.
conversion, with dibromoaniline 1e being the only de-
Moreover, we have found that even activated aro-
tectable minor product (Table 1, run 2). Under opti- matic amines can be selectively monobrominated
mized conditions (Table 1, run 3), the reaction was under appropriate conditions. The reaction with 4-bu-
completed in 4 h with 96% selectivity for monobro- tylaniline (2a) is faster than that with aniline itself
moanilines (1b/1cꢀ1/4). However, it should be em- and gives ortho-brominated product 2b in ca. 85% se-
phasized that if the reaction is allowed to progress lectivity at near 90% conversions (runs 4–6) with di-
further, di- and polybrominated products appear. brominated product 2e being the main minor product
Thus, the reaction must be followed by regular GC (selectivity of 10%). Once again, in spite of the deac-
analyses in order to stop stirring and heating as soon tivating effect of the electron-withdrawing bromine
Scheme 2. Oxidative bromination of aromatic amines.
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Copper-Catalyzed Oxybromination and Oxychlorination
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Scheme 3. Mechanism proposed for the oxybromination of aromatic amines.
substituent, monobrominated product 2b can undergo nism also operates in the copper-catalyzed oxybromi-
further bromination; therefore, the reaction has to be nation of anilines.
stopped in time to avoid polybromination.
A proposed mechanism is presented in Scheme 3
On the other hand, copper-catalyzed oxybromina- using for simplicity aniline itself as the substrate and
tion of deactivated anilines is not complicated at all para-bromoaniline as the product. A first step consists
by polybromination. Ethyl 4-aminobenzoate (3a) and of the formation of a Lewis acid-base complex A be-
4-aminobenzonitrile (4a), both having electron-with- tween Cu(II) and aniline. Then we suggest the ab-
drawing groups, readily react with lithium bromide straction of a hydrogen atom and electron transfer to
and dioxygen giving exclusively ortho-substituted Cu(II) resulting in radical B, Cu(I) and H+; similar
monobromo derivatives 3b and 4b, respectively. These transformations have been also proposed in other
compounds have been obtained in virtually quantita- copper-catalyzed oxidations and oxidative carbonyla-
tive GC yields (Table 1, runs 7 and 8). Furthermore, tion of amines.[30,31] Tautomeric cyclohexadienyl radi-
when stirring and heating were continued for 20 h cal C reacts with Cu(II) bromide giving Cu(I) bro-
after a complete conversion of these substrates, no mide and brominated product D, whose tautomeriza-
significant changes in product compositions were de- tion gives para-bromoaniline 1c. Re-oxidation of
tected. Thus, in this case, the presence of the electron- Cu(I) complexes by dioxygen readily occurs in acetic
withdrawing bromine atom attached to the aromatic acid solutions and completes a catalytic cycle.
nucleus in the primarily formed products suppresses
In general, several concurrent transformations can
their further bromination. It is important to note that occur with the tautomeric radicals B and C, e.g.,
the reactivity of deactivated anilines in oxybromina- carbon-nitrogen and nitrogen-nitrogen coupling to
tion is distinctly different from the behavior of deacti- afford polyanilines[34] and azobenzene,[30] respectively.
vated phenols, which have shown no reaction under Therefore, it is especially remarkable that a high se-
similar conditions.[29] Interestingly, an N-substituted lectivity for the brominated products is observed in
aniline, i.e., N-methylaniline (5a), exhibited very low this work. It seems that the rate-determining step of
reactivity in this reaction (Table 1, run 9).
the reaction is the formation of radicals B and C,
Under the conditions of run 1 in Table 1 but in the whereas their bromination occurs faster. Radicals C
absence of LiBr, only N-phenylacetamide 6 was seem to be rapidly trapped by bromine atoms and
slowly formed. On the other hand, in the absence of have no time for other transformations.
Cu(II) salts no reaction at all occurred with aniline.
Moreover, when Cu(OAc)2 was substituted by Co- be favored by electron-donating groups attached to
(OAc)2, the formation of brominated products was the aromatic nucleus and disfavored by electron-with-
The electron transfer from aniline to Cu(II) should
AHCTREUNG
ACHTREUNG
completely inhibited. These results show an important drawing ones. Indeed, 4-butylaniline is more reactive
and specific role of the copper catalyst in the oxybro- than aniline itself, whereas deactivated anilines 3a
mination reaction. It is also important that air can be and 4a are less reactive. This feature of the process
used as an oxygen source, although the reaction seems to account for the extremely high selectivity
occurs at a lower rate (Table 1, run 10).
for the monobromination of 3a and 4a: primarily
Although the mechanism of this new reaction is not formed monobrominated anilines 3b and 4b are addi-
clear so far, some suggestions could be made based tionally deactivated and undergo no bromination at
on the available information. Only few examples of all under the reaction conditions. Even in the case of
selective copper-catalyzed oxidative transformations activated aniline 2a, excellent control over polybromi-
of amines have been reported to date, with most of nation can be achieved by the appropriate choice of
them being described as free-radical processes with- reaction variables.
[30–33]
À
out the involvement of direct Cu C bonds.
It
Within the proposed mechanistic scheme, it is not
seems reasonable to suggest that a free radical mecha- obvious why N-methylation affects so drastically the
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Luciano Menini et al.
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Table 2. Copper-catalyzed transformations of aromatic amines under oxychlorination conditions.[a]
Run
Substrate
Time [h]
Conversion [%]
Product selectivity[b]
Monochlorination
Acetoxylation
(6 or 8)
[c]
(1d or 2d)
(7)
Smono
ACHTREUNG
1
4
aniline (1a)
1.5
2.5
15
2
15
24
30
57
100
30
100
43
38
31
2
20
2
15
17
50
–
–
–
53
48
52
20
2
47
43
48
75
80
–
4-butylaniline (2a)
5
ethyl 4-aminobenzoate (3a)
–
–
[a]
Conditions: solvent – acetic acid, [substrate]=0.40M; [CuCl2]=0.05M; [LiCl]=0.80M; 1008C; O2 (1 atm). Conversion
and selectivity were determined by GC.
Selectivities based on reacted substrate.
[b]
[c]
Combined selectivity for monochlorinated products (anilines and acetamides).
reactivity of the aniline in oxybromination (Table 1, cause its nitrogen lone-pair electrons are delocalized
run 9). Although N-methylaniline (pKa =4.8) is more by overlap with the neighboring carbonyl group.[35]
basic than aniline (pKa =4.6) and should form a more Thus, the formation of the intermediate complex with
stable complex with Cu(II), the abstraction of the hy- Cu(II), analogous to complex A in Scheme 3, as well
drogen atom from this complex seems to be less fa- as the electron transfer from the substrate molecule
vorable, which could be a possible explanation for the to Cu(II) should be much less favorable in the case of
result obtained.
N-phenylacetamide than with aniline itself.
At the end of the reaction, chloroaniline 1d was
almost completely converted to chloroacetamide 7
(GC yield of ca. 50%), which can be, in a separate
step, easily hydrolyzed by aqueous base back to 1d if
Oxychlorination
We have also examined the behavior of aniline and 4- desired. The only major by-product of this reaction is
butylaniline under oxychlorination conditions, i.e., N-phenylacetamide, also a valuable chemical, so that
using LiCl as a halogen source (Table 2). Surprisingly, the method can be synthetically useful.
the conversions of these substrates were slower than
An activated amine, i.e., 4-butylaniline 2a, gives
in the presence of LiBr and corresponding chlorinated mainly corresponding acetamide 8 under similar con-
derivatives, i.e., 4-chloroaniline (1d) and 2-chloro-4- ditions, with 2-chloro-4-butylaniline 2d being ob-
butylaniline (2d) appeared only as minor products.
served in significant amounts only at low conversions.
NMR and GC/MS identification of the products No chlorinated acetamide, analogous to 7, was detect-
isolated from the reaction mixtures has shown that a ed in the reaction solutions (Table 2, run 2). On the
main transformation of amines 1a and 2a which com- other hand, ethyl 4-aminobenzoate 3a, a substrate
petes with oxychlorination is N-acetoxylation giving having a deactivating electron-withdrawing substitu-
N-phenylacetamide (6) and N-(4-butylphenyl)acet- ent, reacts much slower (Table 2, run 3). A 43% con-
amide (8), respectively. In the case of aniline, mono- version was observed in 24 h; however, only very
chlorinated acetamide 7 was also detected in the reac- small amounts of several unidentified products were
tion solution, with its amounts accounting for ca. 50% detected by GC, the main part of this substrate was
of the mass balance at the end of the reaction converted into high-boiling compounds not detectable
(Table 2, run 1). This product seems to be a result of by GC, probably, oligomers and polymers.
the N-acetoxylation of primarily formed 4-chloroani-
line 1d rather than chlorination of N-phenylacet-
A
lectivities for 1d were observed; at longer reaction
times the amounts of 1d decreased, whereas the In summary, we have developed a highly selective
amounts of 7 increased (Table 2, run 1). On the other method for the oxidative monobromination of unpro-
hand, acetamide 6 was gradually accumulated in the tected aromatic primary amines, both activated and
course of the reaction and its selectivity remained deactivated, under mild aerobic conditions. The use
near 50%. This can be easily explained within the re- of an inexpensive and easy to handle copper catalyst
action mechanism proposed in Scheme 3. The amido and lithium bromide as a halogen source as well as
group, NH
A
and much less basic than the amino group, NH2, be- practical advantage. Oxychlorination of aniline can
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Copper-Catalyzed Oxybromination and Oxychlorination
FULL PAPERS
(CH2), 34.13 (CH2), 134.33 (C4), 109.30 (C2 and C6), 132.08
(C3 and C5), 141.64 (C1).
also be performed under similar conditions, albeit
with lower selectivities. This simple catalytic method
represents an attractive synthetic pathway to expen-
sive low-volume aromatic haloamines. Further studies
are targeted towards the development of solid copper
catalysts resistant to leaching in polar solvents in
order to facilitate catalyst separation.
1
Ethyl 2-bromo-4-aminobenzoate (3b): H NMR: d=1.38
3
3
(t, 3H, CH3, J=7.1 Hz), 4.46 (q, 2H, CH2, J=7.1 Hz), 6.74
(d, 1H, C6H, 3J=8.3 Hz), 7.79 (d, 1H, C5H, 3J=8.3 Hz),
8.12 (s, 1H, C3H); 13C NMR: d=14.25 (CH3), 60.54 (CH2),
107.20 (C2), 114.11 (C6), 120.63 (C4), 130.00 (C5), 134.22
(C3), 148.15 (C1), 165.56 (C=O).
1
2-Bromo-4-aminobenzonitrile (4b): H NMR: d=6.75 (d,
3
3
1H, C6H, J=8.3 Hz), 7.35 (d, 1H, C5H, J=8.3 Hz), 7.68 (s,
1H, C3H); 13C NMR: d=107.84 (C2), 101.15 (C4), 114.80
(C6), 119.47 (CN), 132.47 (C5), 136.43 (C3), 148.19 (C1).
N-Phenylacetamide (6): MS: m/z (rel. int.)=135 (57)
Experimental Section
All reagents were purchased from commercial sources and
used as received. The reactions were carried out in a stirred
glass reactor equipped with a condenser and followed by
measuring a dioxygen uptake and by gas chromatography
(GC) using a Shimadzu 17 instrument fitted with a Carbo-
wax 20 m capillary column and a flame ionization detector.
[M]+, 93 (100); H NMR: d=2.16 (s, 3H, CH3), 7.09 (t, 1H,
1
C4H, J=7.6 Hz), 7.30 (d, 2H, C3H and C5H, J=7.6 Hz),
3
3
7.51 (d, 2H, C2H and C6H, J=7.6 Hz); 13C NMR: d=24.50
3
(CH3), 119.75 (C2 and C6), 124.33 (C4), 128.96 (C3 and C5),
137.96 (C1), 168.67 (C=O).
N-(4-Chlorophenyl)acetamide (7): MS: m/z (rel. int.)=
171 (9) [M+2]+, 169 (27) [M]+, 129 (33), 127 (100), 100 (9);
1H NMR: d=2.14 (s, 3H, CH3), 7.25 (br.s, 2H), 7.48 (br.s,
2H); 13C NMR: d=24.35 (CH3), 121.26 (C2 and C6), 128.86
(C3 and C5), 129.40 (C4), 136.74 (C1), 169.18 (C=O).
N-(4-butylphenyl)acetamide (8): MS: m/z (rel. int.)=191
(46) [M]+, 149 (29), 106 (100); 1H NMR: d=0.90 (t, 3H,
General Procedure
In a typical run, a solution of the aromatic compound
(4.0 mmol, 0.40M), dodecane (225 mL, 1.0 mmol, 0.10M, in-
3
ternal standard), Cu(OAc)2 (0.5 mmol, 0.05M), and LiBr
G
CH3, J=7.2 Hz), 1.29–1.40 (m, 2H, CH2), 1.47–1.58 (m, 2H,
3
(8 mmol, 0.80M) (or CuCl2 and LiCl) in acetic acid (10 mL)
was intensively stirred under oxygen (1 atm) at 60–1008C
for a specified time. A GC mass balance was based on the
substrate charged and calculated using dodecane as an inter-
nal standard.
CH2), 2.07 (s, 3H, COCH3), 2.52 (t, 2H, CH2, J=7.2 Hz),
7.23 (br.s, 2H, C3H and C5H), 7.42 (br.s, 2H, C2H and C6H);
13C NMR: d=13.95 (CH3), 22.30 (CH2), 24.21 (COCH3),
33.66 (CH2), 35.06 (CH2), 120.30 (C2 and C6), 128.64 (C3 and
C5), 135.96 (C4), 138.67 (C1), 168.95 (C=O).
Products were isolated by column chromatography (silica)
and characterized by H and 13C NMR spectroscopy (Bruker
1
DRX-400, tetramethylsilane, CDCl3, COSY, HMQC, DEPT
and NOESY experiments). The structures of some products
were confirmed by GC/MS (Hewlett–Packard MSD 5890/
Series II, 70 eV).
Acknowledgements
1
3
2-Bromoaniline (1b): H NMR: d=6.53 (t, 1H, C4H, J=
We acknowledge a financial support from the CNPq and FA-
PEMIG (Brazil) and scholarships from CNPq (LM and
JCCS). The authors wish to thank Dr. Ivana S. Lula for help
with the NMR measurements, Luciana A. Parreira for experi-
mental assistance, and Amauri G. de Souza for help with the
GC/MS analyses.
3
3
7.8 Hz), 6.63 (d, 1H, C6H, J=7.8 Hz), 7.01 (t, 1H, C5H, J=
3
7.8 Hz), 7.32 (d, 1H, C3H, J=7.8 Hz); 13C NMR: d=109.03
(C2), 115.38 (C6), 124.24 (C4), 128.16 (C5), 132.35 (C3),
143.95 (C1).
4-Bromoaniline (1c): H NMR: d=6.51 (d, 2H, C2H and
1
3
3
C6H, J=8.2 Hz), 7.22 (d, 2H, C3H and C5H, J=8.2 Hz).
13C NMR: dC =110.19 (C4), 116.77 (C2 and C6), 131.80 (C3
and C5), 145.09 (C1).
4-Chloroaniline (1d): MS: m/z (rel.int.)=129 (32) [M+ References
2]+, 127 (100) [M]+, 100 (24), 92 (24), 65 (25).
1
2,4-Dibromoaniline (1e): H NMR: d=6.45 (d, 1H, C6H,
3J=8.6 Hz), 7.36 (d, 1H, C5H, 3J=8.6 Hz), 7.49 (s, 1H,
C3H); 13C NMR: d=109.53 (C2), 109.61 (C4), 121.67 (C6),
131.18 (C5), 134.41 (C3), 143.47 (C1).
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2-Bromo-4-butylaniline (2b): 1H NMR: d=0.90 (t, 3H,
3
CH3, J=7.1 Hz), 1.29–1.40 (m, 2H, CH2), 1.47–1.58 (m, 2H,
CH2), 2.46 (t, 2H, CH2, J=7.2 Hz), 6.64 (d, 1H, C5H, J=
3
3
3
7.3 Hz), 6.89 (d, 1H, C6H, J=7.3 Hz), 7.21 (s, 1H, C3H):
13C NMR: d=13.94 (CH3), 22.25 (CH2), 33.40 (CH2), 34.13
(CH2), 108.79 (C2), 115.91 (C6), 128.37 (C5), 131.58 (C3),
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2,6-Dibromo-4-butylaniline (2e): 1H NMR: d=0.90 (t,
3
3H, CH3, J=7.1 Hz), 1.29–1.40 (m, 2H, CH2), 1.47–1.58 (m,
2H, CH2), 2.46 (t, 2H, CH2, J=7.2 Hz), 7.17 (s, 2H, C3H
3
and C5H); 13C NMR: d=13.94 (CH3), 22.25 (CH2), 33.40
Adv. Synth. Catal. 2008, 350, 2052 – 2058
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