A general and simple method for the synthesis of star-shaped thiophene derivatives

Article abstract of DOI:10.1055/s-1999-2895

One pot synthesis of 1, 3, 5-tris(thienyl)benzene derivatives via tetrachlorosilane mediated trimerization reaction is described.

Full text of DOI:10.1055/s-1999-2895

LETTER
1621
A General and Simple Method for the Synthesis of Star-Shaped Thiophene
Derivatives1
Sambasivarao Kotha,* Kakali Chakraborty, Enugurthi Brahmachary
Department of Chemistry, Indian Institute of Technology, Powai, Mumbai-400 076, India
E-mail: srk@ether.chem.iitb.ernet.in
Received 13 August 1998
the PPHs. In this regard, we attempted tetrachlorosilane
Abstract: One pot synthesis of 1, 3, 5-tris(thienyl)benzene deriva-
(SiCl4) mediated trimerization of 2-acetylfuran and found
tives via tetrachlorosilane mediated trimerization reaction is de-
that a complex mixture of products was formed. In view
of the ring opening reactions of furan under acidic condi-
tions, this result was not surprising to us.
scribed.
Key words: thiophenes, acylation, tetrachlorosilane, polycyclics;
trimerization
Substituted thiophenes are valuable building blocks in
many natural and non-natural products and enjoy poten-
tial applications in flavor and pharmaceutical industries.2
In addition to these synthetic implications, thiophenes oc-
cur abundantly as structural units in many natural mole-
cules.3 Raney nickel desulfurization has made thiophenes
Scheme 1
as useful intermediates for the preparation of the aliphatic
compounds.4 Moreover, a number of substituted
thiophenes are apt to give sulfones, yielding non-aromatic
Since, thiophene derivatives are more stable to various
compounds which undergo Diels-Alder reaction to gener-
Lewis acid conditions, we next tried the trimerization re-
action of 2-acetylthiophene 4 which can be prepared by
treatment of thiophene with acetic anhydride / phosphoric
acid at 70-75 oC.13 Treatment of 4 with SiCl4 at room tem-
perature gave 1 in 42% yield after chromatography. After
completion of our work1 preparation of compound 1 is re-
ported by an indirect route involving Pd mediated cou-
pling reaction as a key step.14 However, attempts to
trimerize 2-acetylthiophene 4 using nafion-H gave no
condensation product.15 Our methodology to these com-
ate the polycyclics.5, 6
Due to the intractable nature of polythiophene (PT) there
is a need to modify PT to make it as processible as con-
ventional organic polymers.7 Oligothiophenes are useful
model systems for PT and in this regard Garnier and co-
workers8 have shown that the semiconducting properties
of PT are already present in α-conjugated sexithienyl. For
design of the new generation of polymers more knowl-
edge is required for the monomer preparation.
In connection with our interest in unusual amino acids pounds is straightforward and involves inexpensive start-
preparation via building block approach9 we conceived ing materials.
the building blocks containing C3-symmetry element is an
After successful trimerization of 4 with SiCl4, we decided
attractive option.1 In this regard, we identified cyclotri-
to generalize this reaction with other thiophene deriva-
merization of carbonyl compounds as a useful strategy.10
tives. Various acetylated thiophenes (5-7 and 9) were pre-
Some of these C3-symmetric building blocks are also use-
pared via alkylation16 and acetylation13 sequence (eq 1).
ful in the preparation of dendrimer molecules11 and
Compound 9 was prepared according to the literature pro-
fullerene fragments.12 For example, oxidation of 1 fol-
cedure.17
lowed by Diels-Alder reaction with the appropriately sub-
stituted acetylenic dienophiles is expected to give
inaccessible 1, 3, 5-triphenyl benzene derivatives (e.g., 3,
Scheme 1).10 Compound 2 is a useful starting material for
the synthesis of C3-symmetric amino acids by asymmetric
derivatization of glycine moiety. Similarly, monoacetyla-
tion and trimerization of compound 1 may generate mixed
aryl-thienyl oligomer. Our attempts to use repetitive
acetylation and trimerization sequence starting from ace-
tophenone to generate dendrimers via 3 was not realized
due to the insoluble nature of polyphenyl hydrocarbons
(PPHs). At this juncture we reasoned out that the heteroar-
omatic systems may obviate the problems associated with
Equation 1
Recently, Hiyama et al. prepared compound 18 via palla-
dium-catalyzed cross-coupling of organosilicon com-
pounds.18 However, we have adopted palladium-
catalyzed cross-coupling reaction19 of phenylboronic acid
20
and 2-acetyl-5-bromothiophene 1421 to obtain 15 (mp.
Synlett 1999, No. 10, 1621–1623 ISSN 0936-5214 © Thieme Stuttgart · New York

1622
S. Kotha et al.
LETTER
o
109-110 C) in 88% yield (eq 2). Along similar lines, one of the most important aspects in the design of liquid
coupling of 4-bromoacetophenone 16 and 2-thiophenebo- crystalline materials.23
o
ronic acid 1720 gave compound 18 (mp. 115-116 C) in
92% yield (eq 3).
Acknowledgement
We acknowledge the RSIC-Mumbai for recording the spectral data
(NMR and Mass). KC and EB thank IIT-Bombay and CSIR-New
Delhi respectively for the fellowships. We also thank Prof. T. K.
Chandrashekar (IIT-Kanpur) for providing some experimental de-
tails for the preparation of 2, 2’-bithiophene.
Equation 2
References and Notes
(1) A portion of this work was presented in 6th NOST meeting,
Lonavala, April 20-23, 1997; Kotha, S.; Brahmachary, E.;
Sreenivasachary, N.; Chakraborty, K. Synthesis of Non-Coded
α-Amino Acids via Building Block Approach.
(2) Hale, K. J.; Manaviazar, S. In Rodd’s Chemistry of Carbon
Compounds; Second Supplements to the 2nd Edition, Vol.
Equation 3
IVA, Sainsbury, M, Ed, Elsevier, New York, 1997, 337 pp;
Thiophene and Its Derivatives, Part 5, Gronowitz, S, Ed, John
Wiley, New York, 1992.
In a typical experimental procedure, acetyl thiophene de-
rivative (0.04 mol) was treated with SiCl4 (2-18 equiva-
lents) in absolute ethanol (40 ml) at 0 oC and the reaction
mixture was stirred at ambient temperature. At the conclu-
sion of reaction (TLC), the dark reaction mixture was
poured into ice cold water and extracted with dichlo-
romethane. Combined organic extracts were washed with
water and then dried over MgSO4. Evaporation of the sol-
vent and purification of the crude product by column
chromatography (silica gel) using hexane as a eluent fur-
nished the trimerized product. The trimerization results of
(3) Kagan, J. In Progress in the Chemistry of Organic Natural
Products, Vol 56, Herz, W.; Grisebach , H.; Kirby, G. W.;
Tamm, Ch, Eds, Springer-Verlag, New York, 1991, 87 pp.
(4) Meyers, A. I. Heterocyclics in Organic Synthesis, John Wiley,
New York, 1974.
(5) O’Donovan, A. R. M.; Shepherd, M. K. Tetrahedron Lett.
1994, 35, 4425.
(6) Simpkins, N. S. Sulphones in Organic Synthesis, Pergmon
Press, New York, 1993.
(7) Kaeriyama, K. In Handbook of Organic Conductive
Molecules and Polymers, Vol 2, Nalwa, H. S, Ed, John Wiley,
New York, 1997, 271 pp.
(8) Horowitz, G.; Fichou, D.; Peng, X.; Xu, Z.; Garnier, F. Solid.
St. Commun. 1989, 72, 381.
1
acetyl thiophene derivatives are shown in the Table. H
NMR and appropriate number of signals in 13C NMR
spectra confirmed the presence of C3 symmetry in all the
trimerized products presented in the Table.♦
(9) Kotha, S.; Brahmachary, E.; Sreenivasachary, N.;
Tetrahedron Lett. 1998, 39, 4905.
(10) For recent examples related to trimerization of corbonyl
compounds see: Elmorsy, S. S.; Khalil, A. G. M.; Girges, M.
M.; Salama, T. A. J. Chem. Res. 1997 (S) 232; (M) 1537 and
references cited therein; Plater, M. J. J. Chem. Soc. Perkin
Trans. 1, 1997, 2897.
Compound 20 was independently synthesized by the pall-
diam mediated coupling of 17 with tribromo derivative 21
in 14% isolated yield (eq 4).
(11) Chow, H-F.; Mong,T.K.-K.; Nongrum, M. F.; Wan, C-W.
Tetrahedron 1998, 54, 8543.
(12) Mehta, G.; Surya Prakash Rao, H. Tetrahedron 1998, 54,
13325.
(13) Kosak, A. I.; Hartough, H. D. Org. Synth. Coll. Vol. 3, 14,
1955.
(14) Pelter, A.; Jenkins, I.; Jones, D. E. Tetrahedron 1997, 53,
10357.
(15) Yamato, T.; Hideshima, C.; Tashiro, M.; Prakash, G. K. S.;
Olah, G. A. Catalysis Lett. 1990, 6, 341.
(16) Ramanathan, V.; Levine, R. J. Org. Chem. 1962, 27, 1667.
(17) Rebstock, M. C.; Stratton, C. D. J. Am. Chem. Soc. 1955, 77,
3082.
Equation 4
(18) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Heterocycles 1990,
30, 303.
(19) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(20) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. S.
Application of Transition Metal Catalysts in Organic
Synthesis, Springer, Berlin, 1998, 13 pp.
In conclusion, we have shown that various acetylated
thiophene derivatives undergo trimerization reaction to
generate C3-symmetric building blocks which may find
useful applications in catalysis22 and organic synthesis.
Availability of mixed aryl-thienyl oligomers where the
thiophene unit is present either in inner or outer core of the
(21) Karlsson, O. Synth. Commun. 1981, 11, 29.
molecule (e.g., 19 and 20) by one-pot reaction may pro- (22) Bolm, C.; Sharpless, K. B. Tetrahedron Lett. 1988, 29, 5101;
Burk, M. J.; Harlow, R. L. Tetrahedron Lett. 1990, 29, 1462.
(23) Daoust, G.; Leclerc, M. Macromolecules 1991, 24, 455.
vide easy access to novel polymer and dendrimer prepara-
tion. In addition, thiophenes bearing an alkyl group are
Synlett 1999, No. 10, 1621–1623 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A General and Simple Method for the Synthesis of Star-Shaped Thiophene Derivatives
1623
Table
♦
Selected spectral data for trimerized products.
1 cm-1; 13 (mp 180 oC dec.) δ 121.6, 123.9, 124.7 (3C?), 128.0,
135.4, 137.3, 137.5, 141.9; UV (CHCl3) λmax=357 nm,
=82108 M-1 cm-1; 19 (mp 244-245 oC) δ 121.9, 124.0, 124.8,
125.7, 127.7, 128.9, 134.1, 135.6, 142.6, 144.3; UV (CHCl3)
λmax=339 nm, =72795 M-1 cm-1; 20 (mp 224-225 oC) 1H
NMR (300 MHz, CDCl3) δ 7.12 (m, 3H), 7.32 (m, 3H), 7.40
(m, 3H), 7.75 (s, 12H), 7.84 (s, 3H); UV (CHCl3) λmax=315
nm, =91175 M-1 cm-1.
13C NMR (75 MHz, CDCl3): 1 (mp 154-155 oC, Lit 14 mp:
156-158 oC ) δ 122.8, 123.9, 125.4, 128.2, 135.7, 143.6; UV
(CHCl3) λmax=296 nm, =50359 M-1 cm-1; 2 (mp 137-139 oC)
δ 15.5, 121.4, 123.5, 126.3, 135.8, 140.0, 141.3; UV (CHCl3)
λ
max=305 nm, =7905 M-1 cm-1; 10 (mp 40-42 oC) δ 13.9,
22.3, 30.0, 33.8, 121.4, 123.3, 125.1, 135.8, 141.0, 146.2; UV
(CHCl3) λmax=306 nm, =32472 M-1 cm-1; 11 (mp 38-39 oC)
δ 14.2, 22.8, 29.2, 29.3, 29.4, 30.4, 31.8, 31.9, 121.5, 123.3,
125.0, 135.8, 141.0, 146.2; UV (CHCl3) λmax=306 nm,
=48543 M-1 cm-1; 12 (mp 177-179 oC) δ 122.0, 123.3, 127.3,
130.2, 135.3, 141.5; UV (CHCl3) λmax=304 nm, =52595 M-
Article Identifier:
1437-2096,E;1999,0,10,1621,1623,ftx,en;L09299ST.pdf
Synlett 1999, No. 10, 1621–1623 ISSN 0936-5214 © Thieme Stuttgart · New York