Cross coupling of polybromoiodobenzenes with some terminal alkynes

Article abstract of DOI:10.1134/S1070428008090121

Sonogashira reactions of pentabromoiodobenzene and tetrabromo-1,4- diiodobenzene with various terminal alkynes at 20°C in benzene resulted in selective replacement of the iodine atoms with formation of the corresponding alk-1-yn-1-yl-substituted polybromobenzenes.

Full text of DOI:10.1134/S1070428008090121

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 9, pp. 1323–1326. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.N. Shishkin, I.V. Tarasova, D.A. Khlevin, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 9, pp. 1339–1342.
Cross Coupling of Polybromoiodobenzenes
with Some Terminal Alkynes
V. N. Shishkin†, I. V. Tarasova, and D. A. Khlevin
Ogarev Mordovian State University, ul. Bol’shevistskaya 68, Saransk, 430000 Russia
e-mail: tarasova_iv_mrsu@mail.ru
Received October 12, 2007
Abstract—Sonogashira reactions of pentabromoiodobenzene and tetrabromo-1,4-diiodobenzene with various
terminal alkynes at 20°C in benzene resulted in selective replacement of the iodine atoms with formation of the
corresponding alk-1-yn-1-yl-substituted polybromobenzenes.
DOI: 10.1134/S1070428008090121
We previously showed [1] that nucleophilic re-
placement of bromine in reactions of polybromoaro-
matics with nucleophiles is almost always accom-
panied by side reductive debromination with participa-
tion of solvent molecules as source of hydrogen.
Moreover, in some cases, reductive debromination
becomes the main reaction pathway. For example, the
reaction of hexabromobenzene with sodium acetylide
in liquid ammonia gives exclusively the corresponding
reductive debromination product, 1,2,4,5-tetrabromo-
benzene [2]. Therefore, synthesis of functional deriva-
tives of the polybromoaromatic series via direct nucle-
ophilic replacement of bromine in polybromobenzenes
by ethynyl groups seems to be improbable.
3,6-diiodobenzene (II) with some terminal alkynes
under the Sonogashira reaction conditions [6]. All re-
actions were carried out in benzene at 20°C under
argon using bis(triphenylphosphine)palladium(II)
chloride as catalyst, copper(I) iodide as co-catalyst,
and triethylamine as base. The initial polybromoiodo-
benzenes were synthesized by iodination of the corre-
sponding polybromobenzenes in the system I2–KIO3–
concd. H2SO4 [7]. As terminal alkynes we selected
prop-2-yn-1-ol (III), prop-2-yn-1-yl acetate (IV),
phenylacetylene (V), and prop-2-yn-1-yl ethers VI and
VII having a polybrominated benzene ring [2].
Br
Br
CH
Br
Br
O
Br
Br
In the recent years, substitution of halogen in aryl
halides via cross coupling reactions catalyzed by
transition metal complexes has been extensively
studied [3]. In most cases, such reactions with poly-
bromoaromatic compounds lead to exhaustive replace-
ment of all bromine atoms in the aromatic ring. Analo-
gous reactions with polyiodoarenes occur much more
readily and under milder conditions. It was noted that
the reactivity of aryl iodides is higher by 5–6 orders of
magnitude than the reactivity of the corresponding aryl
bromides [4, 5]. Taking the above stated into account,
we anticipated that cross coupling with aromatic com-
pounds containing simultaneously bromine and iodine
atoms should result in preferential or exclusive re-
placement of the iodine atoms.
O
CH
Br
Br
Br
Br
VI
VII
Compounds I and II failed to react with prop-2-yn-
1-ol (III): after 24 h, only the initial polybromoiodo-
benzenes were isolated from the reaction mixtures. No
reaction occurred between these compounds on pro-
longed heating. However, in the presence of even
traces of oxygen hexa-2,4-diyne-1,6-diol was always
formed as a result of oxidative dimerization of prop-2-
yn-1-ol. Prop-2-yn-1-yl acetate (IV) is less prone to
undergo oxidative dimerization, and the reaction of IV
with halogen derivatives I and II gave the corre-
sponding cross-coupling products even in the presence
of traces of oxygen in the reaction mixture. The reac-
tion of IV with I in 24 h afforded acetate VIIIa in 23%
In the present work we examined cross coupling of
pentabromoiodobenzene (I) and 1,2,4,5-tetrabromo-
†
Deceased.
1323

SHISHKIN et al.
1324
Scheme 1.
Br
Br
Br
R
Pd(PPh3)2Cl2, PPh3, CuI
Et3N, benzene, 20°C
Br
Br
I
Br
Br
+
R
CH
Br
Br
Br
I
VIIIa–VIIId
Br
Br
R
Pd(PPh3)2Cl2, PPh3, CuI
Et3N, benzene, 20°C
Br
I
I
Br
+
R
CH
Br
Br
Br
R
Br
II
IXa–IXd
VIII, IX, R = MeC(O)OCH2 (a), Ph (b), C6Br5OCH2 (c), C6Br5CH2OCH2 (d).
yield (Scheme 1). The yield of VIIIa increased to 33%
when the reaction time was prolonged to 48 h, but the
yield was not improved upon further increase of the
reaction time and the amount of catalyst. At 80°C the
yield of VIIIa reached 44%, but the reaction was
accompanied by replacement of bromine atoms, which
complicated isolation of the target product from the
reaction mixture. Thus raising the temperature reduces
the selectivity of cross coupling. By analogous reaction
of compound II with prop-2-yn-1-yl acetate (IV)
(reaction time 48 h) we obtained 34% of diacetate IXa
as a result of replacement of both iodine atoms
(Scheme 1). Cross couplings of compounds I and II
with alkynes V−VII were performed under the same
conditions (only the reaction time was varied), and
compounds VIIIb–VIIId and IXb–IXd were formed
in satisfactory yields.
DMSO-d6 using hexamethyldisiloxane as internal
reference. Thin-layer chromatography was performed
on Silufol UV-254 plates using hexane–ethyl acetate
(20:1) as eluent; spots were detected by treatment with
iodine vapor or under UV light. The purity of the
initial compounds and reaction products was checked
by GLC on a Chrom-42 chromatograph equipped with
a thermal ionization detector and a glass column,
3000×3.5 mm, packed with 3% of OV-17 on Chroma-
ton N-Super (0.16–0.20 mm); oven temperature 220–
260°C; carrier gas nitrogen. All individual compounds
had a purity of no less than 97.5–98.5%.
Pentabromobenzene [8], prop-1-yn-1-yl acetate
(IV) [9], 3-(2,3,4,5,6-pentabromophenyloxy)prop-1-
yne (VI) [2], and 3-(2,3,4,5,6-pentabromobenzyloxy)-
prop-1-yne (VII) [2] were synthesized according to
known procedures.
Thus the proposed conditions ensure selective cross
coupling with replacement of only iodine atoms in
polybromoiodoaromatic compounds. The described
approach demonstrates broad synthetic potential of
polybromoiodobenzenes. Introduction of ethynyl frag-
ments into polybromoarene molecules makes them
promising precursors of other classes of organic com-
pounds containing a polybrominated benzene ring,
which could be obtained by transformations involving
the triple bond.
1,2,4,5-Tetrabromobenzene. A solution of AlBr3 in
bromine [0.6 g (0.02 mol) of aluminum was burned in
45 ml (0.9 mol, 140 g) of bromine] was diluted with
200 ml of anhydrous carbon tetrachloride and added
under stirring to 17 ml (0.2 mol, 14.9 g) of anhydrous
benzene so that to avoid strong heating (the flask was
cooled with an ice–water mixture). When the addition
was complete (~ 1 h), the mixture was stirred for
30 min at 20°C and for 2 h at 50–60°C. Excess
bromine was distilled off together with carbon tetra-
chloride, and the precipitate was filtered off, washed
with a 10% solution of Na2SO3 and water, dried in air,
and recrystallized from toluene. Yield 33 g (44%),
colorless crystals, mp 180–182°C; published data [10]:
mp 181°C. IR spectrum, ν, cm−1: 3068 m, 1740 w,
1445 m, 1421 s, 1293 m, 1111 m, 1020 s, 880 s, 668 m,
EXPERIMENTAL
The IR spectra were recorded in KBr on an Infra-
1
LYuM FT-02 instrument. The H NMR spectra were
measured on a Bruker AC-200 spectrometer at an op-
erating frequency of 200 MHz) from solutions in
1
521 m, 433 m. H NMR spectrum: δ 7.87 ppm, s.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

CROSS COUPLING OF POLYBROMOIODOBENZENES
1325
Found, %: C 18.36; H 0.49. C6H2Br4. Calculated, %:
C 18.31; H 0.51.
trum, δ, ppm: 2.04 s (3H, CH3), 4.79 s (2H, CH2).
Found, %: C 24.02; H 0.94. C11H5Br5O2. Calculated,
%: C 23.23; H 0.89.
Pentabromoiodobenzene (I). A mixture of 2.5 g
(0.01 mol) of KIO3, 17.7 g (0.07 mol) of iodine, and
50 ml of concentrated sulfuric acid was stirred for
30 min, a suspension of 12 g (0.02 mol) of penta-
bromobenzene in 100 ml of concentrated sulfuric acid
was added, and the mixture was stirred for 7 days at
18−20°C. It was then poured onto ice, a 10% solution
of Na2SO3 was added to remove excess iodine, and the
precipitate was filtered off, dried over H2SO4 with
protection from light, and recrystallized from benzene.
Yield 15 g (98%), colorless needles, mp 315–317°C;
published data [11]: mp 318°C. IR spectrum, ν, cm−1:
1284 s, 1249 m, 1242 m.
1,2,3,4,5-Pentabromo-6-(phenylethynyl)benzene
(VIIIb). Reaction time 24 h; yield 53%, colorless crys-
tals, mp 80−81°C (from hexane). IR spectrum, ν, cm−1:
2147 w, 1550 m, 1522 m, 1483 m, 1367 m, 1294 m,
1159 m, 1024 w, 914 m, 854 m, 754 s, 721 w, 684 s,
540 w, 524 m. 1H NMR spectrum: δ 7.34–7.66 ppm, m
(C6H5). Found, %: C 30.12; H 0.76. C14H5Br5. Calcu-
lated, %: C 29.36; H 0.88.
1,2,3,4,5-Pentabromo-6-[3-(2,3,4,5,6-penta-
bromophenyloxy)prop-2-yn-1-yl]benzene (VIIIc).
Reaction time 72 h; yield 48%, colorless crystals,
mp 280−281°C (from petroleum ether). IR spectrum,
ν, cm−1: 2970 w, 2928 w, 2866 w, 2851 w, 1508 m,
1435 m, 1419 m, 1334 s, 1184 m, 1157 m, 1118 s,
1060 m, 999 s, 933 m, 721 m, 694 m, 682 m. 1H NMR
spectrum: δ 4.98 ppm, s (CH2). Found, %: C 19.21;
H 0.28. C15H2Br10O. Calculated, %: C 18.07; H 0.20.
1,2,4,5-Tetrabromo-3,6-diiodobenzene (II). A mix-
ture of 5.1 g (0.02 mol) of KIO3, 42.6 g (0.17 mol) of
iodine, and 60 ml of concentrated sulfuric acid was
stirred for 30 min, a suspension of 12 g (0.03 mol) of
1,2,4,5-tetrabromobenzene in 72 ml of concentrated
sulfuric acid was added, and the mixture was stirred
for 5 days at 18−20°C. The mixture was then treated as
described above in the synthesis of pentabromoiodo-
benzene (I) to isolate 12.7 g (82%) of compound II as
colorless long needles with mp 328–330°C; published
data [6]: mp 330°C. IR spectrum, ν, cm−1: 1278 s,
1244 m, 1228 m.
1,2,3,4,5-Pentabromo-6-[3-(2,3,4,5,6-penta-
bromobenzyloxy)prop-2-yn-1-yl]benzene (VIIId).
Reaction time 96 h; yield 62%, colorless crystals,
mp 293−295°C (from petroleum ether). IR spectrum,
ν, cm−1: 2939 w, 2878 w, 1508 m, 1435 m, 1323 m,
1188 m, 1118 m, 1080 s, 1057 m, 995 w, 748 w,
721 m, 694 m, 540 s. 1H NMR spectrum, δ, ppm: 4.41 s
(2H, CH2), 4.99 s (2H, CH2). Found, %: C 19.52;
H 0.51. C16H4Br10O. Calculated, %: C 19.00; H 0.40.
Reactions of polybromoiodobenzenes I and II
with alkynes III−VII (general procedure). A solution
of 0.77 mmol of polybromoiodobenzene I or II in
80 ml of anhydrous benzene was purged with argon,
5 ml of triethylamine, 0.1 g (0.52 mmol) of CuI, and
0.77 mmol (in the reactions with I) or 1.54 mmol (in
the reactions with II) of alkyne III–VII were added,
the mixture was stirred for 10–15 min, 0.02 g
(1 mol %) of Pd(PPh3)2Cl2 and 0.04 g (0.015 mmol) of
PPh3 were added, and the mixture was purged again
with argon, and stirred at 18−20°C until the reaction
was complete. The solvent was removed under reduced
pressure, the residue was dried in air, and the products
were isolated by extraction into hexane or petroleum
ether; in some cases, the products were additionally
purified by flash chromatography on silica gel using
hexane–ethyl acetate (20:1) as eluent.
3-[4-(3-Acetoxyprop-2-yn-1-yl)-2,3,5,6-tetra-
bromophenyl]prop-2-yn-1-yl acetate (IXa). Reaction
time 48 h; yield 34%, colorless crystals, mp 69−71°C
(from petroleum ether). IR spectrum, ν, cm−1: 2253 w,
1749 s, 1442 m, 1377 m, 1221 s, 1159 w, 1032 m,
1020 m, 879 m, 723 w, 696 w, 603 w, 542 m, 522 w.
1H NMR spectrum, δ, ppm: 2.04 s (3H, CH3), 4.79 s
(2H, CH2). Found, %: C 31.96; H 1.67. C16H10Br4O4.
Calculated, %: C 32.80; H 1.72.
1,2,4,5-Tetrabromo-3,6-bis(phenylethynyl)ben-
zene (IXb). Reaction time 24 h; yield 44%, colorless
crystals, mp 152−154°C (from hexane). IR spectrum,
ν, cm−1: 2145 w, 1483 m, 1437 m, 1020 m, 914 m,
1
879 w, 848 w, 754 s, 723 w, 684 s, 524 m. H NMR
spectrum: δ 7.56–7.61 ppm, m (C6H5). Found, %:
C 45.02; H 1.68. C22H10Br4. Calculated, %: C 44.49;
H 1.70.
3-(2,3,4,5,6-Pentabromophenyl)prop-2-yn-1-yl
acetate (VIIIa). Reaction time 48 h; yield 33%, color-
less crystals, mp 23−25°C (from petroleum ether). IR
spectrum, ν, cm−1: 2191 w, 1747 s, 1552 w, 1437 m,
1375 m, 1221 s, 1161 m, 1120 m, 1030 m, 866 w,
1,2,4,5-Tetrabromo-3,6-bis[3-(2,3,4,5,6-penta-
bromophenyloxy)prop-1-yn-1-yl]benzene (IXc).
Reaction time 48 h; yield 72%, colorless crystals,
1
829 w, 750 w, 723 m, 696 m, 542 s. H NMR spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

SHISHKIN et al.
1326
mp 280−281°C (from hexane). IR spectrum, ν, cm−1:
2972 w, 2910 w, 2162 w, 1379 w, 1334 s, 1321 s,
1080 w, 1001 m, 978 m, 960 m, 914 w, 792 w, 733 w,
694 w, 669 w, 626 w, 557 w. H NMR spectrum:
δ 4.98 ppm, s (CH2). Found, %: C 21.13; H 0.48.
3. Handbook of Organopalladium Chemistry for Organic
Synthesis, Negishi, E.-i. and de Meijere, A., Eds., New
York: Wiley, 2002.
1
4. Tao, W., Nesbitt, S., and Heck, R.F., J. Org. Chem.,
1990, vol. 55, p. 63.
5. Bong, D.T.-Y., Gentric, L., Holmes, D., Matzger, A.J.,
Scherhad, F., and Vollhardt, K.P.S., Chem. Commun.,
2002, p. 278.
C24H4Br14O2. Calculated, %: C 20.58; H 0.55.
1,2,4,5-Tetrabromo-3,6-bis[3-(2,3,4,5,6-penta-
bromobenzyloxy)prop-1-yn-1-yl]benzene (IXd).
Reaction time 48 h; yield 80%, colorless crystals,
mp 173−175°C (from hexane). IR spectrum, ν, cm−1:
2943 w, 2889 w, 2125 w, 1514 m, 1419 m, 1323 s,
1186 m, 1084 s, 1060 m, 1020 m, 993 w, 879 m, 721 w,
6. Sonogashira, K., Tohda, Y., and Hagihara, N., Tetra-
hedron Lett., 1975, p. 4467.
7. Lu, J., Ho, D.M., Volelaar, N.J., Kraml, C.M., and
Pascal, R.A., J. Am. Chem. Soc., 2004, vol. 126,
p. 11168.
1
669 m, 607 w, 542 m. H NMR spectrum, δ, ppm:
8. Furuyama, E. and Fudzi, Yu., J. Synth. Org. Chem.,
Jpn., 1971, vol. 29, p. 92; Ref. Zh., Khim., 1971,
no. 16Zh162.
4.40 s (2H, CH2), 4.99 s (2H, CH2). Found, %: C 21.52;
H 0.46. C26H8Br14O2. Calculated, %: C 21.23; H 0.55.
9. Vartanyan, R.S., Kazaryan, Zh.V., and Kucherov, V.F.,
REFERENCES
Arm. Khim. Zh., 1974, vol. 24, p. 295.
10. Qwist, W. and Wikman, H., Acta Acad. Abo., Math.
Phys., 1959, p. 1.
1. Shishkin, V.N., Tarasova, I.V., and Butin, K.P., Izv. Ross.
Akad. Nauk, Ser. Khim., 2005, p. 2305.
11. Deacon, G.B., Farguharson, G.J., and Miller, J.M., Aust.
J. Chem., 1977, vol. 30, p. 1013.
2. Tarasova, I.V., Cand. Sci. (Chem.) Dissertation, Nizhnii
Novgorod, 2006.
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