"conjugate" substitution of hydrogen in the methyl group of pentabromotoluene in the presence of strong bases

Article abstract of DOI:10.1007/s11176-005-0404-x

The reactions of pentabromotoluene with i-PrONa or t-BuONa in pyridine give N-(pentabromobenzyl)pyridinium bromide and a mixture of isomeric tetrabromotoluenes. In the presence of bromine or carbon tetrabromide, the reductive debromination is blocked, and the reactions involve exclusively substitution of hydrogen in the methyl group of pentabromotoluene by the pyridinium residue.

Full text of DOI:10.1007/s11176-005-0404-x

Russian Journal of General Chemistry, Vol. 75, No. 8, 2005, pp. 1243 1246. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 8, 2005,
pp. 1312 1315.
Original Russian Text Copyright
2005 by Shishkin, Vakaeva, Butin.
Conjugate Substitution of Hydrogen in the Methyl Group
of Pentabromotoluene in the Presence of Strong Bases
V. N. Shishkin*, S. S. Vakaeva*, and K. P. Butin**
* Ogarev Mordovian State University, Saransk, Mordovia, Russia
** Lomonosov Moscow State University, Moscow, Russia
Received June 16, 2004
Abstract The reactions of pentabromotoluene with i-PrONa or t-BuONa in pyridine give N-(pentabromo-
benzyl)pyridinium bromide and a mixture of isomeric tetrabromotoluenes. In the presence of bromine or
carbon tetrabromide, the reductive debromination is blocked, and the reactions involve exclusively substitution
of hydrogen in the methyl group of pentabromotoluene by the pyridinium residue.
Previously we found that pentabromotoluene
C6Br5CH3 (I) reacts with MeONa in pyridine to form,
along with tetrabromo(methoxy)toluenes, isomeric
tetrabromotoluenes, as well as compounds in which
the methoxy group substitutes both bromine in the
aromatic nucleus and hydrogen in the methyl group
[1]. This finding suggests concurrent protophilic
attacks of the methoxide anion by the methyl group
of substrate I, whose possibility is provided by the
relatively high acidity of the methyl group (by polaro-
graphic estimates, pKa 16 [2]). Such transformation
opens the way to the synthesis of functional deriva-
tives containing a polybromoaromatic residue via
conjugate substitution of hydrogen in the methyl
group of polybromomethylbenzenes, by-passing
intermediate synthesis of polybromobenzyl bromides.
The conjugate substitution of hydrogen in the
methyl group of pentabromotoluene can be presented
by the reaction sequence (1) (4).
C6Br5CH2 + BH,
C6Br5CH3 + B
(1)
(2)
BH
C6Br5CH2Br + [C6Br4CH3]
C6Br4HCH3,
II
C6Br5CH2
[Br+]
(3)
(4)
II,
C6Br5CH2Br + Nu
C6Br5CH2Nu Br+.
Reaction (1) is an acid base reaction that provides
the pentabromobenzyl anion. The latter as a soft base
abstracts bromine as a positively charged species from
another pentabromotoluene molecule to form penta-
fluorobenzyl bromide (II) and dehydrobromination
products [reaction (2)]. Presumably, with a more
effective donor of [Br+] than pentabromotoluene (I),
reaction (2) will be blocked. In this case, the major
reaction pathway will involve formation of pentabro-
mobenzyl bromide (II) [reaction (3)] whose reaction
with nucleophilic reagents will give -bromine substi-
tution products [reaction (4)].
studied transformations of compound I in pyridine in
the presence of t-BuONa, since in this case bromine
substitution in the polybromoaromatic nucleus with
such a sterically hindered nucleophile is unlikely [3].
The composition of the reaction products was deter-
mined by a combination of GLC, TLC, and prepara-
tive isolation of individual compounds, as well as, in
certain cases, by H and IR spectroscopy. The reaction
conditions and product compositions are listed in the
table.
1
As seen from the table, the conversion of com-
pound I in its reaction with a double excess of
t-BuONa in pyridine is 42% within 1 h (exp. no. 1).
To obtain evidence for his hypothesis, we have
1070-3632/05/7508-1243 2005 Pleiades Publishing, Inc.

1244
SHISHKIN et al.
Reaction of pentabromotoluene (I) with sodium alkoxides RONa in pyridine (115 C, 1 h)
Exp.
no.
Conversion of substrate I,
RONa, additive I: RONa: additive ratio
Identified reaction productsa
%
1
2
3
4
5
6
7
8
t-BuONa
t-BuONa
i-PrONa
i-PrONa
i-PrONa, Br2
i-PrONa, Br2
i-PrONa, Br2
i-PrONa, CBr4
1: 2
1: 4
1: 2
1: 4
1: 4: 2
1: 8: 6
1: 10: 6
1: 2: 2
42
89
67
100
44
26
IV + V + VI (0.31), III (0.14), VII (traces)
IV + V + VI (0.46), III (0.02), VII (traces)
IV + V + VI (0.49), III (0.31), VII (traces)
IV + V + VI (0.5), III (0.06), VII (traces)
IV + V + VI (0.37), III (0.22)
IV + V + VI (0.19), III (0.74)
17
35
IV
+ V + VI (traces), III (0.97)
III (0.94), VII (traces)
a
The yield, mol, per 1 mol of reacted compound I.
As reaction products we identified (2,3,4,5,6-penta-
NMR data, 2,3,5,6-tetrabromotoluene (IV) (73.5%),
2,3,4,6-tetrabromotoluene (V) (24.5%), and 2,3,4,5-
tetrabromotoluene (VI) (2%).
bromobenzylpyridinium) bromide (III) and a mixture
1
of isomeric tetrabromotoluenes, that comprises, by H
+
CH2N
CH3
CH3
CH3
CH2NH2
Br5
Br
Br
Br Br
Br
Br
Br
Br
Br
Br
Br5
Br
Br
Br
III
IV
V
VI
VII
As seen from the composition of tetrabromoto-
luenes, pentabromotoluene is primarily dehydrobro-
minated para to the methyl group, which corresponds
to the combined polar effect of the substituents in the
benzene ring of the substrate. In addition, unidentified
compounds and traces of pentabromobenzylamine
(VII) are formed.
of pentabromobenzylpyridinium bromide in the
presence of t-BuONa or i-PrONa.
Note that in exp. nos. 1 and 2 we recovered un-
reacted compound I, which is probably associated
with substantial steric hindrances to reaction of the
polybromoaromatic compound to t-BuONa. Therefore,
we took for the base the less sterically congested i-
PrONa. Actually, the latter faster reacted in the same
conditions (exp. no. 3). However, here, too, ca. 30%
of unreacted pentabromotoluene (I) was obtained.
With a greater excess of i-PrONa (1:4), the conver-
sion of substrate I was near 100%.
Increased excess of t-BuONa increases the conver-
sion of compound I, but the fraction of pyridinium
salt III in the reaction products sharply decreases
compared with tetrabromotoluenes (exp. no. 2). Mo-
reover, the fraction of unidentified products, too,
increases. This result can be explained by further trans-
formations of salt III. The heteroring cleavage in
pyridinium derivatives under the action of nucleo-
philes, forming polymethines, is well known [4, 5].
In this connection we can suggest that in the reaction
in hand, too, the pyridinium ring in salt III is cleaved
under the action of excess t-BuONa. Evidence for this
suggestion comes from the presence of trace amounts
of pentabromobenzylamine (VII) among the reaction
products. Amine VII was formed by decomposition
In should be noted that in exp. no. 4, like in
exp. no. 2, the fraction of salt III in the reaction
products decreases compared with tetrabromotoluenes,
on account of decomposition of the salt in the
presence of excess base.
The formation of tetrabromotoluenes and penta-
bromobenzylpyridinium bromide (III) suggests that
this process includes reactions (1), (2), and (4), and
the role of nucleophile here is played by the pyridine
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 8 2005

CONJUGATE SUBSTITUTION OF HYDROGEN IN THE METHYL GROUP
1245
itself [reaction (4)]. In no one experiment we detected
pentabromobenzyl isopropyl ether and bis(pentabro-
mobenzyl) ether (the latter can be formed by reaction
of pentabromobenzyl bromide with t-BuONa [6]).
About 0.5 mol of a mixture of tetrabromotoluenes is
formed per 1 mol of reacted compound I (exp.
nos. 2 4), which corresponds to the theoretical yield
by Eqs. (1) and (2).
(3000 3.5 mm, stationary phase Chromaton N-Super
(0.16 0.20 mm) + 3% OV-17, oven temperature 220
260 C, carrier gas nitrogen.
Isomeric tetrabromotoluenes [2], pentabromoto-
luene [9], pentabromobenzyl bromide [9], pentabromo-
benzyl isopropyl ether [6], and bis(pentabromobenzyl)
ether [6] were synthesized by described procedures.
To trap the pentabromobenzyl anion formed we
used bromine. The reaction in the presence of Br2
provides more salt III and less tetrabromotoluenes
(exp. nos. 5 7), implying blocking of reaction (2),
that enhances with increasing amount of Br2 and gets
complete when the I:RONa:Br2 ratio is 1:10:6.
Evidence for this conclusion comes from the absence
among the reaction products of tetrabromotoluene and
the formation of ca. 1 mol of salt III per 1 mol of
reacted substrate I (exp. no. 7), which corresponds to
the theoretical yield of salt III in the reaction
sequence (1), (3), and (4).
(2,3,4,5,6-Pentabromobenzyl)pyridinium bro-
mide (III). A mixture of 50 ml of pyridine and 5 g of
pentabromobenzyl bromide (II) was heated under
reflux for 4 h. The precipitate was filtered off, washed
with dioxane, dried, and recrystallized from water.
Yield 90%, decomp. point 264 265 C. IR spectrum
1
(KBr), , cm : 3050 w, 3029 w, 2998 m, 2990 m,
2952 w, 2836 w, 1624 s, 1512 w, 1497 m, 1476 v.s,
1429 m, 1346 w, 1321 m, 1304 w, 1287 w, 1229 w,
1186 m, 1156 m, 1148 m, 1063 w, 938 w, 777 m,
1
735 w, 685 w, 675 w, 480 w. H NMR spectrum
(DMSO-d6), , ppm: 6.36 s (2H, CH2C6Br5), 8.12
8.31 m (2H, H2,6), 8.62 8.77 m (1H, H4), 8.94
9.16 m (2H, H3,5).
In his case, the source of [Br+] can be both the
bromine itself and isopropyl hypobromite i-PrOBr
formed by bromine reaction with i-PrONa [7]. Note-
worthy is the great amount of unreacted pentabromo-
toluene (I), which may be associated with a deficit of
the base. Probably, the i-PrOBr formed under the re-
action conditions reacts with excess i-PrONa to form
propene oxide and other compounds [7].
Reaction of pentabromotoluene (I) with bases in
pyridine (see table). A mixture of 200 ml of pyridine
and 0.02 mol of compound I was heated until the
latter dissolved completely, after which required
amounts of bases and additives were added. The re-
sulting mixtures were heated under reflux for 1 h,
treated with water, and neutralized with HCl. The
precipitate was filtered off, washed with water, and
dried. Reaction products were extracted with hot
dioxane, the extract was evaporated, and the residue
was analyzed by TLC, GLC, and 1H NMR. The
residue undissolved in hot dioxane was salt III (by IR
spectroscopy).
For the donor of [Br+] we also used CBr4 [8]. In
this case, at C6Br5CH3 :CBr4 = 1:2 in the same condi-
tions we isolated no other products than salt III and
traces of amine VII (exp. no. 8). The absence in the
reaction products of tetrabromotoluenes suggests
complete blocking of reaction (2). However, with
CBr4 as the source of [Br+], the substrate conversion,
too, is rather low (35%).
REFERENCES
It is interesting to note that in dioxane or CCl4 as
solvents and in the presence of a phase-transfer
catalyst no deprotonation of pentabromotoluene was
observed.
1. Shishkin, V.N., Lapin, K.K., Tanaseichuk, B.S., and
Butin K.P., Zh. Org. Khim., 1988, vol. 24, no. 3, p. 577.
2. Butin, K.P., Ivkina, A.A., Shishkin, V.N., and Reu-
tov, O.A., Vestn. Mosk. Gos. Univ., Ser. 2: Khim., 1983,
vol. 24, no. 4, p. 382.
EXPERIMENTAL
3. Shishkin, V.N., Lapin, K.K., Olenina, N.V., and Bu-
The IR spectra were obtained on an InfraLYUM
FT-02 instrument. The H NMR spectra were ob-
tained on Bruker AM-300 (300 MHz) and Bruker
DPX-400 (400 MHz) instruments in CDCl3 and
DMSO-d6, internal reference HMDS.
tin, K.P., Zh. Org. Khim., 1999, vol. 35, no. 7, p. 1056.
1
4. Heterocyclic Compounds, Elderfield, R.C., Ed., New
York: Wiley, 1952, vol. 1. Translated under the title
Geterotsiklicheskie soedineniya, Moscow: Inostran-
naya Literatura, 1953, vol. 1, p. 312.
Gas chromatography was performed on a Chrom-
42 chromatograph, thermoionic detector, glass column
5. Comprehensive Organic Chemistry, Barton, D.H. and
Ollis, W.D., Eds., Oxford: Pergamon, 1979, vol. 4.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 8 2005

1246
SHISHKIN et al.
Translated under the title Obshchaya organicheskaya
8. Bromine Compounds: Chemistry and Applications,
khimiya, Moscow: Khimiya, 1982, vol. 8, p. 15.
Price, D. and Iddon, D., Eds., 1988, vol. 11, p. 145.
6. Shishkin, V.N., Vakaeva, S.S., and Butin K.P., Zh. Org.
Khim., 2002, vol. 38, no. 5, p. 747.
9. Tanaseichuk, B.S., Vasin, V.A., Rumyantseva, K.S.,
Shishkin, V.N., Rumyantsev, N.P., Shishkin, S.N., and
Butin, K.P., Zh. Org. Khim., 1981, vol. 17, no. 6,
p. 1270.
7. Walling, C. and Kjellgren, J., J. Org. Chem., 1969,
vol. 34, no. 5, p. 1487.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 8 2005