A novel one-pot synthesis of different derivatives of tetraarylterephthal aldehyde via a multiple aryne sequence

Article abstract of DOI:10.1055/s-0029-1218593

The synthesis of a novel series of tetraarylterephthalaldehyde derivatives in an one-pot reaction is described. In this methodology 1,2,4,5-tetrachloro-3, 6-diiodobenzene is treated with various aryl Grignard reagents (excess) in tetrahydrofuran to give t

Full text of DOI:10.1055/s-0029-1218593

SHORT PAPER
395
A Novel One-Pot Synthesis of Different Derivatives of Tetraarylterephthal-
aldehyde via a Multiple Aryne Sequence
N
ovel One-Po
a
t
Synthesis
t
of
T
etr
e
a
aryltereph
m
thalaldehydes eh Jabbari,* Akbar Saednya
Faculty of Chemistry, University of Tabriz, Tabriz, Iran
Fax +98(411)340191; E-mail: f_jabary3055@yahoo.com
Received 2 October 2009; revised 26 October 2009
this route. Saednya and Hart reported1 two efficient routes
for the synthesis of m-terphenyls from 1,3-dichloroben-
zene. In the first route, 2,6-dichlorophenyllithium reacted
with aryl Grignard reagents to give m-terphenyls in 57–
Abstract: The synthesis of a novel series of tetraarylterephthalalde-
hyde derivatives in an one-pot reaction is described. In this method-
ology 1,2,4,5-tetrachloro-3,6-diiodobenzene is treated with various
aryl Grignard reagents (excess) in tetrahydrofuran to give tetraaryl-
benzene-1,4-diylbis(magnesium bromides). After reaction of this 93% yield. In the second route, the reaction of 1,3-dichlo-
product with ethyl formate and aqueous quench, tetraaryltereph-
thalaldehydes are isolated in 33–80% yields. A mechanism involv-
ing organometallic aryne intermediates is proposed.
robenzene with excess aryllithium in diethyl ether at room
temperature gave the corresponding m-terphenyls in 59–
94% yields.
Key words: tetraarylterephthalaldehyde, 1,2,4,5-tetrachloro-3,6-
In this work we investigated the reaction of aryl Grignard
diiodobenzene, aryl Grignard reagents, tetraarylbenzene-1,4-diyl-
reagents with 1,2,4,5-tetrachloro-3,6-diiodobenzene (1).
We reasoned that 1 would undergo halogen–metal ex-
change preferentially at iodine to give Grignard 2. When
2 was treated with ethyl formate and then aqueous quench,
tetraarylterephthalaldehydes 3–10 were obtained in good
yields (Table 1).
bis(magnesium bromide), ethyl formate
Tetraarylterephthalaldehydes are polyaromatic hydrocar-
bons that may be of interest in the fields of liquid crystals,
chiral cyclophanes, benzimidazolophanes, and pharma-
ceuticals.1,2
In 1949 Schonberg and Alyismail3 reported the first syn-
thesis of 1,2,4,5-tetraphenylbenzene from the reaction of
chalcone with oxalyl chloride. Breslow and co-workers4
later showed that the reduction of the diphenylcyclopro-
penyl cation with zinc produced bis(diphenylcycloprope-
nyl), which when heated to 135 °C gave 1,2,4,5-
tetraphenylbenzene and 1,2,3,4-tetraphenylbenzene in a
ratio of 10:1.
This new synthesis has the following unique features: (1)
these compounds are synthesized for first time; (2) six
aryl–aryl bonds are formed in a one-pot reaction; (3) the
reaction proceeds via a four-aryne sequence; (4) different
aryl Grignard reagents are used to generate and trap
arynes; (5) substituents are easily incorporated on the cen-
tral ring; (6) the yield of the reaction is good; and (7) sim-
ple and available starting materials are used.
The essence of our method is to use a Grignard reagent to
generate an aryne through metal–halogen exchange and
then to trap it by nucleophilic addition. The Grignard re-
agent is therefore used in excess. Addition of 1,2,4,5-tet-
rachloro-3,6-diiodobenzene (1) in tetrahydrofuran to
phenylmagnesium bromide in the same solvent under re-
flux conditions, followed by stirring for 15 hours gave, af-
ter treatment with ethyl formate and then hydrolysis,
tetraphenylterephthalaldehyde (3) in 46% yield.
A further method for the preparation of these compounds
was reported in 1969 by Bestmann and Denzel;5 it used
the decarboxylation of 2,3-diphenylcycloprop-2-enecar-
boxylic acid to give 1,2,4,5-tetraphenylbenzene in 92%
yield. Various methods have been used by Dodson and
Fan,6 Hoyt and co-workers,7 Weiss and co-workers,8 and
Di Vona and Rosnati9 in low yields. Tetraarylbenzene de-
rivatives can be synthesized by organometallic reactions.
In 1969, Berry and Wakefield treated10 hexabromoben-
zene with magnesium in tetrahydrofuran using 1,2-
dibromoethane as the promoter to give pentabromophe-
nylmagnesium bromide in 32% yield. Later, it was shown
that this conversion could be greatly improved using ex-
change with phenyl- or ethylmagnesium bromide.11 Hart
and co-workers obtained12 good yields of 1,2,4,5-tet-
raphenylbenzene from the reaction of 1,2,4,5-tetrabromo-
3,6-dichlorobenzene with excess phenylmagnesium bro-
mide and using tetrahydrofuran as the solvent; other
1,2,4,5-tetraarylbenzene derivatives were synthesized by
Hence, it is clear that the principle reaction product from
1 and excess phenylmagnesium bromide is tetraphenyl-
benzene-1,4-diylbis(magnesium bromide) (2, Ar = Ph).
The reaction of this product with ethyl formate and hy-
drolysis with water under mild acidic condition, gave the
desired product 3 in 46% yield. Other aryl Grignard re-
agents gave analogous products 4–10, as summarized in
Table 1. All of the products in Table 1 are new com-
1
pounds. Their structures are confirmed by H and 13C
NMR and IR spectra, and elemental analysis. In general,
the yields of tetraarylterephthalaldehydes are good, the
only poor example being 10 which was obtained in 33%
yield (entry 8).
SYNTHESIS 2010, No. 3, pp 0395–0397
Advanced online publication: 07.12.2009
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x
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DOI: 10.1055/s-0029-1218593; Art ID: Z20509SS
© Georg Thieme Verlag Stuttgart · New York

396
F. Jabbari, A.Saednya
SHORT PAPER
Table 1 Synthesis of Tetraarylterephthalaldehydes
MgBr
CHO
I
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Cl
Cl
Cl
Cl
THF
1. HCOOEt
2. H3O+
ArMgBr
(excess)
+
reflux, 15 h
Ar
MgBr
CHO
I
2
3–10
1
Entry
Ar
Ph
Product
Yield (%)
Mp (°C)
1
2
3
4
5
6
7
8
3
4
46
61
50
62
80
40
68
33
340–341
317–319
270–273
312–313
>360
4-MeC6H4
4-MeOC6H4
4-FC6H4
5
6
4-ClC6H4
7a
8
3-MeOC6H4
3-MeC6H4
4-PhC6H4
205
9
246–247
366–367
10
a The condition of this reaction was stirring at room temperature for 48 h.
I
MgBr
MgBr
MgBr
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Ar
Cl
ArMgBr
– ArI
ArMgBr
– ArI
ArMgBr
Cl
– MgBrCl
– MgBrCl
Cl
Cl
I
I
11
MgBr
MgBr
13
MgBr
1
12
14
MgBr
MgBr
CHO
MgBr
MgBr
Ar
Cl
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Cl
Cl
Ar
ArMgBr
ArMgBr
1. HCOOEt
2. H3O+
Cl
Ar
Ar
MgBr
MgBr
CHO
3–10
15
16
17
18
Scheme 1
The mechanism involves as key intermediates the 1,4-di- dehydes 3–10 can easily be obtained from simple precur-
Grignard reagent 12 and various organometallic arynes as sors in one step.
outlined for 1,2,4,5-tetrachloro-3,6-diiodobenzene in
Scheme 1. Rapid formation of 11 from 1 and arylmagne-
sium bromide is well established. Grignard exchange and
elimination is then repeated to give aryne 17, which is
trapped to give the di-Grignard 18. The mechanism shows
that the major Grignard exchange occurs at iodine not at
chlorine, and di-Grignard formation is essential to the tet-
raarylation reaction. Addition of arylmagnesium bromide
to the intermediate organometallic arynes (i.e., 13, 17,
etc.) occurs regiospecifically always to give 1,4-di-
Grignards and not 1,3-di-Grignards.
1H and 13C NMR spectra were recorded at 400 MHz and 100 MHz,
respectively, on a Bruker-Avance spectrometer using CDCl3 as a
solvent and TMS as an internal standard. Melting points were deter-
mined with an Electrothermal 9100 apparatus and are uncorrected.
FT-IR spectra were obtained on a Bruker-Tensor 27 spectropho-
tometer using KBr pellets. Elemental analysis was recorded on
CHN-Rapid-Hearus apparatus. Anhyd Na2SO4 was the drying re-
agent throughout. Chromatography used silica gel 230–400 mesh.
TLC was carried out using pre-coated plates of Merck silica gel 60
F
254. All reactions were performed under dry argon using reaction
vessels previously dried at 120 °C. THF and Et2O were distilled
from benzophenone sodium ketyl prior to use.
In conclusion, we have found 1 to be a useful tetraaryne
equivalent that reacts with excess Grignard reagent to give
tetraaryl di-Grignards 18. With subsequent addition of
ethyl formate and then hydrolysis, tetraarylterephthalal-
1,2,4,5-Tetrachloro-3,6-diiodobenzene (1)
A soln of 1,2,4,5-tetrachlorobenzene (10.79 g, 49.95 mmol) and I2
(27.9 g, 110 mmol) in oleum (29% SO3, 40 mL) was vigorously
stirred (magnetic) at 60 °C for 3.5 h. The mixture was poured into
Synthesis 2010, No. 3, 395–397 © Thieme Stuttgart · New York

SHORT PAPER
Novel One-Pot Synthesis of Tetraarylterephthalaldehydes
397
ice water and neutralized with 10% aq Na2CO3 and then 10% aq
NaHCO3 and washed with 10% aq sodium bisulfite to remove ex-
cess I2. After extraction with THF and Et2O, the combined organic
layers were dried (Na2SO4). Removal of the solvent gave 1 (10.03
g, 43%) as a white solid; mp 208–209 °C.
13C NMR: d = 191.7, 140.1, 136.8, 133.2, 132.9, 130.6, 127.2.
Anal. Calcd for C32H18Cl4O2: C, 66.6; H, 3.1. Found: C, 65.2; H,
3.1.
Tetra(3-methoxyphenyl)terephthalaldehyde (8)
Mp 205 °C.
Tetraphenylterephthalaldehyde (3); Typical Procedure
A soln of 1 (2.4 g, 5 mmol) in anhyd THF (40 mL) was added slow-
ly over 2 h to a soln of PhMgBr [prepared from PhBr (3.2 mL, 30
mmol), and Mg (1 g, 40 mmol) in THF (40 mL)] and the mixture
was stirred for an additional 15 h at reflux. The reaction was
quenched with ice and it was treated with ethyl formate (10 mL). It
was then cooled in an ice-water bath and quenched with dil HCl.
The aqueous mixture was extracted with THF–Et2O. The combined
organic layers were dried and the solvent evaporated under reduced
pressure. Recrystallization of the residue (Et2O) gave nearly pure 3
(46% yield); mp 340–341 °C.
FT-IR (KBr): 2842, 2739, 1701, 1594, 1244, 1041 cm–1.
1H NMR: d = 9.76 (s, 2 H), 7.18–7.07 (m, 4 H), 6.79–6.52 (m, 12
H), 3.66 (s, 6 H), 3.62 (s, 6 H).
13C NMR: d = 193.7, 158.8, 141.4, 137.6, 128.6, 123.2, 116.0,
115.8, 113.3, 55.1.
Anal. Calcd for C36H30O6: C, 77.4; H, 5.4. Found: C, 77.3; H, 5.5.
Tetra(3-tolyl)terephthalaldehyde (9)
Mp 246–247 °C.
FT-IR (KBr): 2920, 2736, 1704, 1307, 702 cm–1.
FT-IR (KBr): 2843, 2741, 1699, 700 cm–1.
1H NMR: d = 9.67 (s, 2 H), 6.99–6.87 (m, 8 H), 6.77–6.73 (m, 8 H),
2.13 (s, 12 H).
1H NMR: d = 9.73 (s, 2 H), 7.20–7.14 (m, 12 H), 7.05–7.01 (m, 8
H).
13C NMR: d = 193.03, 140.8, 136.6, 135.9, 135.6, 135.3, 130.3,
126.8, 126.6, 126.2, 20.2.
13C NMR: d = 193.8, 141.9, 137.7, 136.4, 130.5, 127.6, 127.2.
Anal. Calcd for C32H22O2: C, 87.6; H, 5.0. Found: C, 87.5; H, 5.3.
Anal. Calcd for C32H30O2: C, 84.4; H, 6.1. Found: C, 85.3; H, 6.1.
Tetra(4-tolyl)terephthalaldehyde (4)
Mp 317–319 °C.
Tetra(biphenyl-4-yl)terephthalaldehyde (10)
Mp 366–367 °C.
FT-IR (KBr): 2923, 2852, 1698, 732 cm–1.
1H NMR: d = 9.86 (s, 2 H), 7.57–7.52 (m, 8 H), 7.46 (d, J = 8.3 Hz,
8 H), 7.41 (t, J = 7.2 Hz, 8 H), 7.32(tt, J = 7.2,1.2, 2 Hz, 4 H) 7.16
(d, J = 8.3 Hz, 8 H).
FT-IR (KBr): 2846, 2735, 1704 cm–1.
1H NMR: d = 9.68 (s, 2 H), 6.97 (d, J = 7.8 Hz, 8 H), 6.89 (d, J = 8
Hz, 8 H), 2.26 (s, 12 H).
13C NMR: d = 194.3, 141.5, 138.3, 136.6, 133.5, 130.4, 128.3, 21.2.
Anal. Calcd for C36H30O2: C, 84.4; H, 6.1. Found: C, 84.4; H, 6.2.
13C NMR: d = 193.9, 141.6, 140.2, 139.9, 131.09, 128.7, 127.4,
126.9, 126.3.
Tetra(4-methoxyphenyl)terephthalaldehyde (5)
Mp 270–273 °C.
Anal. Calcd for C56H38O2: C, 90.5; H, 5.1. Found: C, 88.4; H, 6.8.
FT-IR (KBr): 2842, 2741, 1699, 1514, 1246 cm–1.
1H NMR: d = 9.70 (s, 2 H), 6.92 (d, J = 8.7 Hz, 8 H), 6.71 (d, J = 8.7 Acknowledgment
Hz, 8 H), 3.74 (s, 12 H).
13C NMR: d = 194.4, 158.5, 141.3, 138.6, 131.8, 128.7, 113.1, 55.0.
The authors are indebted to Tabriz university for supporting of this
work and Mrs. Aghazadeh for her helpful suggestions during the
manuscript preparation.
Anal. Calcd for C36H30O6: C, 77.4; H, 5.4. Found: C, 77.0; H, 5.4.
Tetra(4-fluorophenyl)terephthalaldehyde (6)
Mp 312–313 °C.
References
FT-IR (KBr): 2861, 2756, 1747, 1512, 1229 cm–1.
1H NMR: d = 9.70 (s, 2 H), 7.00–6.95 (m, 8 H), 6.91 (t, J = 8.7 Hz,
8 H).
13C NMR: d = 192.1, 160.9 (d, JC4-F = 246.5 Hz), 140.3, 136.9,
131.01 (d, JC2-F = 8.2 Hz), 130.8 (d, JC1-F = 3.5 Hz), 114.03 (d,
JC3-F = 21.5 Hz).
(1) Saednya, A.; Hart, H. Synthesis 1996, 1455.
(2) Chau, J. J.; Hart, H.; Ward, D. L. J. Org. Chem. 1993, 58, 64.
(3) Schonberg, A.; Alyismail, I. J. Chem. Soc. 1942, 585.
(4) Breslow, R.; Gal, P.; Chang, H. W.; Altman, L. J. J. Am.
Chem. Soc. 1965, 87, 5139.
(5) Denzel, Th.; Bestmann, H. J. Tetrahedron Lett. 1969, 10,
3817.
(6) Dodson, R. M.; Fan, J. Y. J. Org. Chem. 1971, 36, 2708.
(7) Hoyt, E. B. Jr.; Reineberg, E. J.; Goodman, P.; Vaughan, P.;
Vlasios, G. Tetrahedron Lett. 1972, 13, 1579.
(8) Weiss, R.; Schlierf, C.; Koelbl, H. Tetrahedron Lett. 1973,
14, 4827.
(9) Di Vona, M.; Rosnati, V. Gazz. Chim. Ital. 1993, 123, 25;
Chem. Abstr. 1993, 119, 95033a.
(10) Berry, D. J.; Wakefield, B. J. J. Chem. Soc. C 1969, 2342.
(11) Smith, C. F.; Moore, G. J.; Tamborski, C. J. Organomet.
Chem. 1971, 33, C21.
MS (EI, 70 eV): m/z (%) = 44 (100), 481 (71), 510 (64), 356 (28).
Anal. Calcd for C32H18F4O2: C, 75.2; H, 3.55. Found: C, 75.2; H,
3.8.
Tetra(4-chlorophenyl)terephthalaldehyde (7)
Following the typical procedure using 1-bromo-4-chlorobenzene
(25 mmol) and Mg (25 mmol) in THF (30 mL) at r.t. for 48 h. When
the mixture was extracted with THF–Et2O or CH2Cl2, the product
precipitated; mp >360 °C.
FT-IR (KBr): 2835, 2742, 1700, 1090, 806 cm–1.
1H NMR: d = 9.67 (s, 2 H), 7.20 (d, J = 8.4 Hz, 8 H), 6.94 (d,
J = 8.4 Hz, 8 H).
(12) Harada, K.; Hart, H.; Du, C. J. F. J. Org. Chem. 1985, 50,
5524.
Synthesis 2010, No. 3, 395–397 © Thieme Stuttgart · New York