Polybromoaromatic compounds: X. Reactions of polybromobenzenes with primary and secondary amines

Article abstract of DOI:10.1023/A:1016382008923

Polybromobenzenes C₆Br₅X (X = Br, F, CN, NO ₂) react with primary amines (methylamine and cyclohexylamine) to give nucleophilic substitution products; reactions of the same substrates with secondary amines (dimethylamine, diethylamine, piperidine, and morpholine) are accompanied by hydrodebromination processes.

Full text of DOI:10.1023/A:1016382008923

Russian Journal of Organic Chemistry, Vol. 38, No. 3, 2002, pp. 374 377. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 3, 2002,
pp. 396 399.
Original Russian Text Copyright
2002 by Shishkin, Esina, Lapin, Butin.
Polybromoaromatic Compounds: X.* Reactions
of Polybromobenzenes with Primary and Secondary Amines
1
1
1
2
V. N. Shishkin , I. V. Esina , K. K. Lapin , and K. P. Butin
1
Ogarev Mordovian State University, ul. Bol’shevistskaya 68, Saransk, 430000 Russia
2
Moscow State University, Vorob’evy gory, Moscow, 119899 Russia
Received May 10, 2001
Abstract Polybromobenzenes C6Br5X (X = Br, F, CN, NO2) react with primary amines (methylamine and
cyclohexylamine) to give nucleophilic substitution products; reactions of the same substrates with secondary
amines (dimethylamine, diethylamine, piperidine, and morpholine) are accompanied by hydrodebromination
processes.
We previously showed that reactions of polybromo-
fluorobenzenes with sodium alkoxides in pyridine
[2, 3] or methanol [4] result exclusively in replace-
ment of the fluorine atom by alkoxy group, in keeping
with the known halogen mobility order in aromatic
nucleophilic substitution (SNAr). However, the major
pathway in the reactions of pentabromofluorobenzene
with morpholine or piperidine is replacement of
bromine by the amine residue, and the process is
accompanied by hydrodebromination to an appreciable
extent [2]. The reasons for such behavior of C6Br5F
in the reactions with morpholine and piperidine are
not clear.
In continuation of our previous studies, in the
present work we examined reactions of substituted
polybromobenzenes C6Br5X (X = Br, F, NO2, CN)
with some primary (methylamine and cyclohexyl-
amine) and secondary amines (dimethylamine, di-
ethylamine, piperidine, and morpholine). The reactions
of C6Br6 and C6Br5F with methylamine, dimethyl-
amine, and diethylamine were carried out in pyridine
under pressure, and those with cyclohexylamine, mor-
pholine, and piperidine, in a large excess of amine
under reflux. The results are given in Tables 1 and 2.
amount of disubstituted products was obtained
(Table 1). The complete conversion of hexabromoben-
zene was observed when the mixture was heated for
8 h at 100 C; in this case the yield of hydrode-
bromination products increased to 6%, the yield of
disubstituted products was 19%, and two unidentified
compounds were formed ( 8%). The reaction of hexa-
bromobenzene with dimethylamine under the same
conditions was even slower. After 15 h, the conver-
sion of C6Br6 was as low as 50%, and the major
product was N,N-dimethylpentabromoaniline; also,
products of reductive debromination were detected.
Diethylamine turned out to be less reactive toward
C6Br6 than dimethylamine. Under the above condi-
tions (15 h, 100 C), the conversion of hexabromoben-
zene did not exceed 40%, and the major products were
those formed by hydrodebromination (Table 1). Also,
up to 25% of a mixture of compounds soluble in sul-
furic acid was found (9 components, according to the
GLC data). Obviously, these compounds contain
an amine residue and their concentrations in the mix-
ture are comparable.
A slow reaction occurred on heating of hexabromo-
benzene with a large excess of cyclohexylamine at
the boiling point. After 5.5 h, the reaction mixture
still contained traces of initial hexabromobenzene.
The products were N-cyclohexylpentabromoaniline
(major), pentabromobenzene ( 2%), and unidentified
compound whose concentration increased as the reac-
tion was prolonged (this compound appeared in the
mixture even at a C6Br6 conversion of 70%).
The reaction of hexabromobenzene with excess
methylamine was fairly slow. After 72 h (20 C), only
initial hexabromobenzene was isolated from the reac-
tion mixture. When the mixture was heated for 5 h at
100 C, the conversion of C6Br6 was 61%, the major
product was N-methylpentabromoaniline, and a small
____________
As follows from the data in Table 1, the reaction
of C6Br6 with amines includes mainly two competing
*
For communication IX, see [1].
1070-4280/02/3803-0374$27.00 2002 MAIK Nauka/Interperiodica

POLYBROMOAROMATIC COMPOUNDS: X.
Table 1. Reactions of hexabromobenzene with amines (Nu)
375
Product composition, %
Time, h
(tempera-
ture, C)
Nucleophile
Nu
Conversion
of C6Br6, %
disubstituted and
C6Br4H2 C6Br5H
C6Br5Nu
C6Br4HNu
unidentified products
CH3NH2
cyclo-C6H11NH2 5.5 (135)
(CH3)2NH
(C2H5)2NH
Piperidine
Morpholine
5
(100)
61
96
40
30
82
74
Traces
Traces
4
23
8
Traces
2
30
53
26
92
94
54
9
5
12
15
15
10
10
(100)
(100)
(106)
(128)
25 (9 substances)
Traces
32
53
33
20
1
26
Traces
Table 2. Reactions of pentabromofluorobenzene with amines (Nu)
Product composition, %
Time, h
(tempera-
ture, C)
Nucleophile
Nu
Conversion
of C6Br6, %
disubstituted and
C6Br4HF C6Br5Nu C6Br4FNu C6Br3HFNu
unidentified products
CH3NH2
cyclo-C6H11NH2
(CH3)2NH
(C2H5)2NH
Piperidine
Morpholine
72
1
6
(20)
(135)
(100)
100
96
71
20
78
76
97
90
34
30
67
28
45
0.5
3
7
55
22
18
32
10 (100)
10 (106)
10 (128)
4
64
71
10
11
Traces
Traces
processes: nucleophilic substitution of bromine by
the amine residue and hydrodebromination. Their
relative contributions are strongly determined by steric
factor. Primary amines (methylamine and cyclohexyl-
amine) give rise mainly to nucleophilic substitution
products. As the size of nucleophile increases, the
contribution of hydrodebromination rises: in the reac-
tions with dimethylamine, piperidine, and morpholine
the contributions of nucleophilic substitution and
hydrodebromination processes are comparable, while
the latter process predominates in the reaction with
diethylamine.
Pentabromofluorobenzene reacts with methylamine
and cyclohexylamine at a much higher rate than does
hexabromobenzene, and the major products are those
formed by replacement of the fluorine atom by the
amine residue (Table 2). The reactions of C6Br5F
with secondary amines (piperidine, morpholine, di-
methylamine, and diethylamine) are accompanied by
hydrodebromination whose contribution ranges from
18 to 61% (it is lesser than in the reactions with hexa-
bromobenzene, where the contribution of hydrode-
bromination ranges from 34 to 75% under analogous
conditions). The main process is nucleophilic substitu-
tion of bromine rather than fluorine atom, and the
rates of the reactions of C6Br5F and C6Br6 with the
above amines (except for dimethylamine) are compar-
able. Unfortunately, we failed to determine the site
of bromine replacement in C6Br5F in reactions with
secondary amines. Probably, the orientation of halo-
gen replacement in reactions of C6Br5F with primary
and secondary amines strongly depends on steric
factors. Primary amines replace the labile fluorine
atom in C6Br5F. In reactions with secondary amines
which are bulkier nucleophiles less labile bromine
atoms in the ortho position with respect to fluorine are
replaced, for they are considerably less shielded than
the fluorine atom having two neighboring bromine
atoms. Analogous change of orientation with increase
in the size of nucleophile was observed in reactions of
pentachlorobenzene with ammonia [5], methylamine
[6], and diethylamine [7], where the contribution of
ortho-substitution (with respect to hydrogen) sharply
increased in the respective order.
Polybromoaromatic compounds C6Br5X reacted
with cyclohexylamine in pyridine (115 C) at a very
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002

376
SHISHKIN et al.
low rate. The conversion of C6Br6 was only 20% in
10 h, whereas the reaction of hexabromobenzene with
sodium methoxide under similar conditions is com-
plete in less than 5 min (the corresponding rate con-
stants differ by more than 5 orders of magnitude [8]).
Strong electron-acceptor groups, such as NO2 and CN,
notably increase the rate of nucleophilic substitution
0.008 (X = F); 2.8 1.8 (X = NO2), 35.6 6 (X = CN);
0.020 0.006 (morpholine, 128 C, X = Br), 0.044
0.011 (X = F); 0.56 0.2 (X = NO2); 7.4 2.4
(X = CN). It is seen that reactions of polybromo-
aromatic compounds with piperidine are faster than
with morpholine; obviously, the reason is that piperi-
dine is a stronger base than morpholine (by 3 orders
of magnitude [11]).
The rates of the reactions of pentabromobenzo-
nitrile with the amines under study exceed those for
the reactions of pentabromonitrobenzene with the
same amines by more than an order of magnitude:
1
in polybromaromatic ring: kap(C6Br5X) 105, l mol
1
s : 0.8 0.3 (X = Br), 27.6 7.8 (X = NO2), 430 12
(X = CN). It should be noted that the reaction of
pentabromonitrobenzene with cyclohexylamine gives
products of replacement of the nitro group and
bromine atom at a ratio of 1:2.5 (according to the
GLC data). The site of bromine replacement was not
determined.
k(C6Br5CN)/k(C6Br5NO2)
12.4 (piperidine), 13.2
(morpholine), 15.8 (cyclohexylamine), though the
cyano group is usually a weaker electron acceptor than
NO2 [11]. These data indicate partial distortion of
conjugation between the nitro group and the aromatic
ring, caused by steric effect of the ortho-bromine
atoms. A similar pattern was observed by us while
studying reactions of analogous polybromoaromatic
compounds with sodium methoxide [12].
The reactions of C6Br5NO2 and C6Br5CN with
piperidine and morpholine were carried out in a way
similar to that reported in [2] for C6Br5F and C6Br6.
Pentabromonitrobenzene reacts with piperidine at
a sufficiently high rate. Even after 1 h, the initial
pentabromonitrobenzene disappears from the reaction
mixture. The major products had very similar reten-
tion times, so that we failed to separate them. In the
1H NMR spectrum of the product mixture we ob-
served a six-proton multiplet signal in the region
1.37 1.87 ppm and three multiplets at 2.45 2.66,
2.66 2.93, and 2.93 3.37 ppm with an overall intens-
ity corresponding to 4 protons. The 1H NMR spectrum
of N-(pentabromophenyl)piperidine (as a possible
product of replacement of the nitro group) contains
two multiplets in the regions 1.45 1.88 ppm (6H,
2 - and -CH2) and 2.90 3.28 ppm (4H, 2 -CH2) [2].
The product mixture showed in the IR spectrum
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
1
trometer in mineral oil. The H NMR spectra were
measured on Tesla BS-467 (60 MHz) and Bruker AC-
200 (200 MHz) instruments using HMDS as internal
(with CCl4 or CDCl3 as solvent) or external reference
(DMSO-d6). The initial compounds, final products,
and reaction mixtures were analyzed by GLC on
a Chrom-42 chromatograph using glass columns
3000 3.5 mm and 1500 3.5 mm, packed with 5% of
OV-17 on Chromaton N-Super (0.16 0.20 mm) and
1
strong absorption bands at 1560 and 1330 cm ,
which are typical of symmetric and antisymmetric 5% of SE-30 on Chromaton N-AW-HMDS (0.16
stretching vibrations of a nitro group in polybromo-
aromatic ring [9, 10]. Thus, the spectral data suggest
that the reaction involves replacement of both bromine
atom and nitro group, but we did not succeed in
estimating the contribution of each of these processes.
Likewise, the reaction of pentabromonitrobenzene
with morpholine led to formation of a complex mix-
ture of products, but at a lower rate. We failed to
isolate any individual product by column chromatog-
raphy on silica gel or aluminum oxide (using hexane
and petroleum ether benzene as eluent) or by gradient
reprecipitation with water from concentrated H2SO4.
0.20 mm); oven temperature 200 260 C; thermoionic
detector; carrier gas nitrogen.
Hexabromobenzene [8], pentabromofluorobenzene
[13], pentabromonitrobenzene [9], pentabromobenzo-
nitrile [9], pentabromoaniline [14], and N-methyl-
pentabromoaniline [12] were synthesized by known
procedures.
N,N-Dimethylpentabromoaniline. A mixture of
2.5 g of pentabromoaniline and 10 ml of freshly dis-
tilled dimethyl sulfate was heated for 3 h at 130 C
under vigorous stirring, 50 ml of a 5% aqueous solu-
tion of NaOH was added, and the mixture was heated
for 0.5 h under reflux. The precipitate was filtered
off, washed with water, dried, and recrystallized from
2-propanol. Yield 2.2 g (87%), mp 80 81 C. IR spec-
We measured the rates of the reactions of some
polybromoaromatic compounds with morpholine and
piperidine using excess reagent as solvent. The kinetic
curves were linear in the coordinates typical of
1
trum, cm : 760 w, 855 m, 1000 s, 1085 w, 1125 w,
1
1
pseudofirst-order reactions, k(C6Br5X) 103, s :
1215 w, 1275 w, 1315 m, 1332 m, 1547 m. H NMR
0.033 0.009 (piperidine, 106 C, X = Br); 0.047
spectrum (CCl4), , ppm: 2.75 s (NMe2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002

POLYBROMOAROMATIC COMPOUNDS: X.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002