Are terminal aryl butadiynes stable? Synthesis and X-ray crystal structures of a series of aryl- and heteroaryl-butadiynes (Ar-C≡C-C≡C-H)

Article abstract of DOI:10.1021/jo0615697

The synthesis and isolation are reported of a range of terminal aryl- and heteroaryl-butadiynes (ArC≡C-C≡CH) 4a-h from 2-methyl-6-(aryl/ heteroaryl)hexa-3,5-diyn-2-ol precursors. The stability of 4a-h in solution is concentration dependent: many of the de

Full text of DOI:10.1021/jo0615697

Are Terminal Aryl Butadiynes Stable? Synthesis and X-ray Crystal
Structures of a Series of Aryl- and Heteroaryl-butadiynes
(Ar-CtC-CtC-H)
Kara West, Changsheng Wang, Andrei S. Batsanov, and Martin R. Bryce*
Department of Chemistry, Durham UniVersity, Durham DH1 3LE, UK
m.r.bryce@durham.ac.uk
ReceiVed July 28, 2006
The synthesis and isolation are reported of a range of terminal aryl- and heteroaryl-butadiynes
(ArCtC-CtCH) 4a-h from 2-methyl-6-(aryl/heteroaryl)hexa-3,5-diyn-2-ol precursors. The stability
of 4a-h in solution is concentration dependent: many of the derivatives can be stored as dilute solutions
for several days or even weeks. The X-ray crystal structures have been obtained for five ArCtC-CtCH
derivatives [Ar ) 2-(9-fluorenonyl), 4-biphenyl, 2-pyridyl, 4-pyridyl, and 2-pyrazyl].
Introduction
targets, which can serve as convenient synthetic reagents for
both symmetric and unsymmetric homologues. They have been
generated by desilylation of trialkylsilylated precursors
(ArCtC-CtCSiR3)8 or by dehydrohalogenation of haloene-
yne(R-CtC-CHdCHCl)9orene-haloyne(R-CHdCH-CtCCl)
derivatives.10 The ArCtC-CtCH species have generally been
used in situ, and it has been frequently stated that they are
unstable to isolation due to their rapid decomposition or
polymerization.8c,11 There are, however, a few exceptions.
Ferrocenylbutadiyne “can be stored as a solid in a refrigerator
under air for several months. However, it does decompose
slowly in solutions.”11e Crystals of 4-tBu-C6H4-CtC-CtCH
are “stable”, and the authors state that “this result was surprising
given the reported instability problems of other phenylbutadiyne
derivatives.”11f A terminal butadiyne functionalized with a
Within contemporary acetylene chemistry,1 there is great
interest in the synthesis of conjugated diyne and oligoyne
molecules. They are fundamentally important carbon-rich build-
ing blocks2 for molecular rods and cyclic frameworks;3 they
are active components in optoelectronic devices (wires, switches
and nonlinear optics, etc.),4 and the extent of intramolecular
π-conjugation within the diyne is a topic of experimental and
theoretical debate.5 Although remarkable oligoyne systems
[R-(CtC)n-R] of nanoscale lengths end-capped with orga-
nometallic6 or silyl substituents7 have been synthesized, simple
terminal aryl butadiynes, ArCtC-CtCH, remain very elusive
(1) Acetylene Chemistry: Chemistry, Biology and Material Science;
Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim,
Germany, 2005.
(2) Carbon-Rich Compounds: From Molecules to Materials; Haley, M.
M., Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim, Germany, 2006.
(3) (a) Bunz, U. H. F.; Rubin, Y.; Tobe, Y. Chem. Soc. ReV. 1999, 28,
107-119. (b) Nielsen, M. B.; Diederich, F. Chem. ReV. 2005, 105, 1837-
1867. (c) Marsden, J. A.; Miller, J. J.; Shirtcliffe, L. D.; Haley, M. M. J.
Am. Chem. Soc. 2005, 127, 2464-2476. (d) Bowling, N. P.; Halter, R. J.;
Hodges, J. A.; Seburg, R. A.; Thomas, P. S.; Simmons, C. S.; Stanton, J.
F.; McMahon, R. J. J. Am. Chem. Soc. 2006, 128, 3291-3302.
(4) Cornil, J.; Beljonne, D.; Calbert, J.-P.; Bre´das, J.-L. AdV. Mater. 2001,
13, 1053-1119.
(5) (a) Rogers, D. W.; Matsunaga, N.; Zavitsas, A. A.; McLafferty, F.
J.; Liebman, J. F. Org. Lett. 2003, 5, 2373-2375. (b) Jarowski, P. D.;
Wodrich, M. D.; Wannere, C. S.; Schleyer, P. v. R.; Houk, K. N. J. Am.
Chem. Soc. 2004, 126, 15036-10537.
(6) Mohr, W.; Stahl, J.; Hampel, F.; Gladysz, J. A. Chem.-Eur. J. 2003,
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(7) (a) Eisler, S.; Chahal, N.; McDonald, R.; Tykwinski, R. R. Chem.-
Eur. J. 2003, 9, 2542-2550. (b) Eisler, S.; Slepkov, A. D.; Elliott, E.; Luu,
T.; McDonald, R.; Hegmann, F. A.; Tykwinski, R. R. J. Am. Chem. Soc.
2005, 127, 2666-2676.
(8) (a) Eastmond, R.; Walton, D. R. M. Tetrahedron 1972, 28, 4591-
4599. (b) Ziessel, R.; Suffert, J. Tetrahedron Lett. 1996, 12, 2011-2014.
(c) Heuft, M. A.; Collins, S. K.; Yap, G. P. A.; Fallis, A. G. Org. Lett.
2001, 3, 2883-2886. (d) Zhou, N.; Merschrod, S. E. F.; Zhao, Y. J. Am.
Chem. Soc. 2005, 127, 14154-14155.
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(b) Liu, L.; Wong, W.-Y.; Poon, S.-Y.; Shi, J.-X.; Cheah, K.-W.; Lin, Z.
Chem. Mater. 2006, 18, 1369-1378. (c) Lewis, J.; Khan, M. S.; Kakkar,
A. K.; Johnson, B. F. G.; Marder, T. B.; Fyfe, H. B.; Wittmann, F.; Friend,
R. H.; Dray, A. E. J. Organomet. Chem. 1992, 425, 165-176.
(10) Karatholuvhu, M. S.; Fuchs, P. L. J. Am. Chem. Soc. 2004, 126,
14314-14315.
10.1021/jo0615697 CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/05/2006
J. Org. Chem. 2006, 71, 8541-8544
8541

West et al.
SCHEME 1a
SCHEME 2a
a Reagents and conditions: (i) 4-tert-butyliodobenzene, Pd(PPh3)2Cl2,
CuI, triethylamine, 45 °C.
a Reagents and conditions: (i) Pd(PPh3)2Cl2, CuI, triethylamine, THF,
20 °C; (ii) NaOH, toluene, reflux.
dithiafulvene unit was reported to be “quite stable”, although it
was not characterized and was homocoupled in situ.12 Our
unexpected finding that crystals of 2-(4-tert-butylphenyl)-5-(4-
butadiynylphenyl)-1,3,4-oxadiazole were stable to storage at
room temperature for at least 2 years13 prompted us to explore
the synthesis of simpler aryl- and heteroaryl-butadiynes.
FIGURE 1. X-ray molecular structures at 120 K (50% thermal
ellipsoids) of 4a, b (independent molecule A), c, e, and f (the ordered
molecule).
were deprotected with loss of acetone17 using a catalytic amount
of NaOH in refluxing toluene. Products 4a-h were thereby
obtained in 60-91% yields after column chromatography. The
survival of 4a-h in this reaction mixture at 110 °C is
remarkable. Phenyl- and 2-thienyl-derivatives 4g and 4h were
the least stable in the series. Nonetheless, NMR analysis of a
solution of 4g (25 mg) in CDCl3 (0.6 mL) stored on the bench
in the daylight at 20 ( 2 °C without exclusion of air revealed
very little decomposition during at least 2 weeks (see Supporting
Information). Refluxing a 5 × 10-2 M solution of biphenyl
derivative 4b in either toluene, cyclohexane, or 1,4-dioxane in
daylight for 10 min resulted in a slight darkening of the solution
and recovery of 60-70% of unchanged 4b (NMR evidence;
see Supporting Information).
The stability of 4a-h in solution is concentration depend-
ent: a general trend is that stability increases with increasing
dilution, as noted by other workers for arylbutadiyne species.11c,f
Amorphous solids of most of the diynes are less stable to storage
at ambient conditions, darkening in color within 24 h at 20 °C,
although their crystalline forms are sufficiently stable for routine
X-ray analysis within a few days of their isolation.
Compound 4g was cross-coupled in situ with 4-tert-butyl-
iodobenzene to afford the expected product 5 in 75% yield based
on 3g (Scheme 2).
X-ray Molecular Structures. X-ray crystal structures were
obtained for derivatives 4a, b, c, e, and f (Figure 1) and
precursors 3a and c (see Supporting Information).
The packing motifs of 4a, c, e, and f are basically similar.
Molecules are linked by tC-H‚‚‚O (4a; Figure 2) or tC-H‚‚‚N
(4c, e, f) (Figure 3 for 4c) hydrogen bonds into infinite chains
zigzagging along the y axis (4a, c) or running parallel to the
(101h) line (4e, f), while in the perpendicular direction they form
slanted stacks of aryl moieties, as well as arrays of parallel diyne
rods, related by the lattice translation a (Figure 4 for 4e).
Structure 4f contains two independent molecules, one of them
disordered equally between two positions differing by
We now report that a range of ArCtC-CtCH derivatives
can be purified under routine conditions and their solutions can
be stored for weeks or even months without significant
decomposition (NMR evidence). The X-ray crystal structures
have been obtained for five ArCtC-CtCH derivatives [Ar
) 2-(9-fluorenonyl), 4-biphenyl, 2-pyridyl, 4-pyridyl, and
2-pyrazyl].
Results and Discussion
Synthesis. Our protocol (Scheme 1) is basically different from
those used in most other laboratories for arylbutadiyne
synthesis,7-10 although phenylbutadiyne has been prepared
previously by a similar method (although not using 2 as a
building block) and used in situ.14 Reaction of the aryl/heteroaryl
iodides 1a-h with 2-methyl-3,5-hexadiyn-2-ol 215 under stan-
dard Sonogashira conditions16 [triethylamine, CuI, Pd(PPh3)2Cl2,
THF, 20 °C] gave precursors 3a-h (75-97% yields), which
(11) For statements on the instability of simple ArCtCCtCH species,
see: (a) Morisaki, Y.; Luu, T.; Tykwinski, R. R. Org. Lett. 2006, 8, 689-
692. This paper states that “aryl butadiynes are unstable to isolation.” (b)
Heuft, M. A.; Collins, S. K.; Yap, G. P. A.; Fallis, A. G. Org. Lett. 2001,
3, 2883-2886. (c) Haley, M. M.; Bell, M. L.; English, J. J.; Johnson, C.
A.; Weakely, T. J. R. J. Am. Chem. Soc. 1997, 119, 2956-2957. (d) Graham,
E. M.; Miskowski, V. M.; Perry, J. W.; Coulter, D. R.; Stiegman, A. E.;
Schaefer, W. P.; Marsh, R. E. J. Am. Chem. Soc. 1989, 111, 8771-8779.
(e) Yuan, Z.; Stringer, G.; Jobe, I. R.; Kreller, D.; Scott, K.; Koch, L.;
Taylor, N. J.; Marder, T. B. J. Organomet. Chem. 1993, 452, 115-120. (f)
Wan, W. B.; Haley, M. M. J. Org. Chem. 2001, 66, 3893-3901 and
references therein. (g) Brandsma, L. Synthesis of Acetylenes, Allenes and
Cumulenes; Elsevier: Amsterdam, 2004; p 360 describes PhCtCCtCH
as “extremely unstable”.
(12) Nielsen, M. B.; Utesch, N. F.; Moonen, N. N. P.; Boudon, C.;
Gisselbrecht, J.-P.; Concilio, S.; Piotto, S. P.; Seiler, P.; Gu¨nter, P.; Gross,
M.; Diederich, F. Chem.-Eur. J. 2002, 8, 3601-3613.
(13) Wang, C.; Pålsson, L.-O.; Batsanov, A. S.; Bryce, M. R. J. Am.
Chem. Soc. 2006, 128, 3789-3799.
(14) Dabdoub, M. J.; Baroni, A. C. M.; Lenarda˜o, E. J.; Gianeti, T. R.;
Hurtado, G. R. Tetrahedron Lett. 2001, 57, 4271-4276.
(15) Gusev, I.; Kucherov, V. F. Bull. Acad. Sci. USSR, DiV. Chem. Sci.
(Engl. Transl.) 1962, 995-999.
(17) The acetone protecting group has been used for the synthesis of
alkylbutadiynes: (a) Carpita, A.; Neri, D.; Rossi, R. Gazz. Chim. Ital. 1987,
117, 481-489. (b) Dabdoub, M. J.; Dabdoub, V. B.; Lenarda˜o, E. J.
Tetrahedron Lett. 2001, 42, 1807-1809.
(16) Marsden, J. A.; Haley, M. M. In Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004; Vol. 1, Chapter 6.
8542 J. Org. Chem., Vol. 71, No. 22, 2006

Series of Aryl- and Heteroaryl-butadiynes
FIGURE 2. Crystal packing of 4a, showing hydrogen bonds (dashed
lines). The repeat vectors of the diyne array (dotted lines) equal the
lattice vector a (3.79 Å) and form an angle of ca. 68.5° with the diyne
rod.
FIGURE 5. Crystal packing of 4b, projected on the (010) plane.
1
Molecules of type A (blue) lie at z ≈ /2, and those of type B (red) lie
1
at z ≈ /4. Nonacetylenic H atoms are omitted.
succession of herringbone layers parallel to the (010) plane
(Figure 5). There are no continuous arrays of diyne groups, only
isolated (A‚‚‚B) dimers with d ) 5.32 Å and Φ ) 63.5°. In 4b,
the molecular “rod” is slightly bent: the angle between the
C(11)‚‚‚C(14) and C(9)-C(10) vectors equals 3.4°, and that
between the C(11′)‚‚‚C(14′) and C(9′)-C(10′) vectors is 9.2°.
Compound 4b is among the most stable of the series, and this
increased stability can be explained by this packing mode, which
will disfavor polymerization.
FIGURE 3. Hydrogen bonding (dashed lines) in the crystal of 4c.
Projection on the (101) plane.
For the most efficient topochemical polymerization of
butadiynes to occur, the guidelines are that the vector between
the diyne centroids should have the length (“repeat distance”,
d) of 4.7-5.2 Å and form an angle (Φ) of ca. 45° with the
diyne rod, such an arrangement bringing the CR atom of one
diyne opposite to the Cδ of the next.20 A nonslanted array, with
every diyne carbon in close contact with its counterparts, is also
favorable.20c Structures 4a, c, e, and f have d ≈ 3.8 Å and Φ )
68-69°, not far from the ideal parameters of the latter
arrangement (d ) 3.4 Å, Φ ) 90°) and practically the same as
in the structures of C6F5CtC-CtCPh (d ) 3.7 Å, Φ ) 75°)
or PhCtC-CtCPh‚C6F5CtC-CtCC6F5 (d ) 3.7 Å, Φ )
72-82°), both of which undergo a neat lattice-preserving
polymerization.20c Indeed, solid-state polymerization without
preservation of crystallinity can occur even with much more
awkward packing. However, it has been shown that structures
outside the general guidelines will not readily react and
molecules that might be chemically labile are kinetically trapped
and thereby stabilized in the crystal lattice.21
FIGURE 4. Crystal packing of 4e, showing hydrogen bonds as dashed
lines (d ) a ) 3.82 Å, Φ ) 68.9°).
a 0.75 Å shift along the direction of the diyne rod as well as
the hydrogen-bonded chain. The average of these two positions
is related to the second (ordered) molecule by a pseudo-inversion
1
1
center (1/2 /4 /2), “upgrading” the actual space group Pn to
pseudo-P21/n.
The asymmetric unit of 4b comprises two molecules, A
and B, whose biphenyl moieties adopt similarly twisted
conformations (dihedral angles 45.6° and 42.6°). Molecules of
type A form zigzag chains through weak hydrogen bonds18
tC-H‚‚‚π(Ph), and molecules of type B form parallel chains
through tC-H‚‚‚π(CtC) bonds.19 The structure is thus a
(20) (a) Baughman, R. H. J. Appl. Phys. 1972, 43, 4362-4370. (b)
Enkelmann, V. Chem. Mater. 1994, 6, 1337-1340. (c) Coates, G. W.; Dunn,
A. R.; Henling, L. M.; Dougherty, D. A.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 248-251.
(18) Malone, J. F.; Murray, C. M.; Charlton, M. H.; Docherty, R.; Lavery,
A. J. J. Chem. Soc., Faraday Trans. 1997, 93, 3429-3436.
(19) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural
Chemistry and Biology; Oxford University Press: Oxford, 1999.
(21) Enkelmann, V. AdV. Polym. Sci. 1984, 63, 91-136.
J. Org. Chem, Vol. 71, No. 22, 2006 8543

West et al.
butadiynes. There is a history of explosions with analogous
compounds in other laboratories, for example, terminal hexatriynes.22
2-(Buta-1,3-diynyl)-9-fluorenone (4a). Compound 3a (0.29 g,
1.01 mmol), NaOH (120 mg), toluene (15 mL), and heating afforded
4a as greenish-yellow needles (0.17 g, 72%) after column chro-
matography (silica, chloroform) and recrystallization from a
chloroform-ethanol mixture. The single crystal (a greenish-yellow
needle) used for X-ray structural analysis was obtained by slow
evaporation of its chloroform solution. 1H NMR (CDCl3, 400 MHz,
298 K): δ 7.77 (s, 1H), 7.68 (d, J ) 6.8 Hz, 1H), 7.64 (d, J ) 8.0
Hz, 1H), 7.53 (s, 1H), 7.51 (m, 2H), 7.34 (t, J ) 7.0 Hz, 1H), 2.54
(s, 1H). 13C NMR (CDCl3, 75 MHz, 333 K): δ 192.2, 144.9, 143.7,
138.9, 134.9, 134.6, 134.5, 129.8, 128.3, 124.6, 122.1, 120.8, 120.3,
75.2, 74.5, 72.2, 68.0. MS (EI) m/z 227.9 (M+, 100%). Anal. Calcd
for C17H8O: C, 89.46; H, 3.53. Found: C, 88.98; H, 3.44. Upon
standing on the laboratory bench at ambient conditions, crystals of
4a gradually turned dark green. The crystals did not have a melting
point at <350 °C. Upon heating the CDCl3 solution (∼15 mg in
Conclusions
In summary, we have synthesized and isolated a range of
terminal aryl- and heteroaryl-butadiynes 4a-h. A general trend
is that stability in solution increases with increasing dilution.
Many of the ArCtC-CtCH derivatives can be stored as dilute
solutions for several days or even weeks, and crystal structures
can be readily obtained within a few days of their preparation.
The shelf-stability of many of these ArCtC-CtCH derivatives
is notable as it is often stated that aryl butadiynes are unstable
to isolation.11 The availability of ArCtC-CtCH species from
readily available precursors should facilitate the synthesis of
new acetylenic scaffolds, molecular rods and cycles, as well as
transition metal complexes of conjugated di- and oligoyne
species.
Experimental Section
1
0.5 mL) at 65 °C, a multiplet H NMR signal at δ ∼7.5 ppm
General Procedure for the Preparation of 3a-h. A mixture
of the iodoarenes 1a-h, 2-methyl-3,5-hexadiyn-2-ol 2,15 Pd(PPh3)2-
Cl2, CuI, and triethylamine (with additional THF for 3a) was stirred
at 20 or 45 °C for 5-18 h, as detailed below. The volatile liquids
were removed by vacuum evaporation, and the residue was
chromatographed on a silica column and/or recrystallized to afford
products 3a-h.
2-(5-Hydroxy-5-methylhexa-1,3-diynyl)-9-fluorenone (3a). 2-Io-
dofluorenone 1a (0.35 g, 1.14 mmol), 2-methyl-3,5-hexadiyn-2-ol
2 (0.25 g, 2.31 mmol), THF (5 mL), Pd(PPh3)2Cl2 (40 mg), CuI
(15 mg), and triethylamine (30 mL) at 20 °C for 5 h gave 3a as
yellow needles (0.32 g, 97%) after column chromatography (silica,
chloroform-diethyl ether 85:15 v/v) and recrystallization from an
ethanol-H2O mixture: mp 157.0-157.8 °C. The single crystal used
for X-ray analysis (orange needle) was obtained by slow evaporation
increased gradually, indicating a structural change of the diyne
group.
1-(4-tert-Butylphenyl)-4-phenylbutadiyne (5). Compound 3g
(0.29 g, 1.53 mmol), NaOH (0.14 g), and toluene (30 mL) afforded
4g as a colorless oil (0.18 g, 1.45 mmol), which was purified by
column chromatography (silica, hexane). Hexane was removed in
vacuo, and without delay this sample of 4g, 4-tert-butyliodobenzene
(0.18 mL, 0.96 mmol), Pd(PPh3)2Cl2 (34 mg), CuI (10 mg), and
triethylamine (50 mL) was mixed and stirred at 45 °C for 18 h to
afford 5 as a yellow solid (0.19 g, 75% from 3g) after column
1
chromatography (silica, dichloromethane): mp 79.7-80.5 °C. H
NMR (CDCl3, 400 MHz): δ 7.55-7.53 (m, Ar-H, 2H), 7.49-
7.47 (m, Ar-H, 2H), 7.38-7.34 (m, Ar-H, 5H), 1.33 (s, (CH3)3,
9H). 13C NMR (CDCl3, 75 MHz): δ 152.8, 132.6, 132.4, 129.2,
128.6, 125.6, 122.1, 118.8, 82.0, 81.3, 74.3, 73.4, 35.1, 31.2. GC-
MS (EI) m/z 259.1 (M+). Anal. Calcd for C20H18: C, 92.98; H,
7.02. Found: C, 92.75; H, 6.96.
1
of its chloroform solution at room temperature. H NMR (CDCl3,
400 MHz): δ 7.72 (s, 1H), 7.66 (d, J ) 7.6 Hz, 1H), 7.58 (dd, J12
) 7.6 Hz, J13 ) 1.2 Hz, 1H), 7.51 (s, 1H), 7.50 (d, J ) 2.2 Hz,
1H), 7.47 (d, J ) 8.0 Hz, 1H), 7.32 (m, 1H), 2.05 (s, 1H), 1.59 (s,
6H). 13C NMR (CDCl3, 100 MHz): δ 192.6, 144.6, 143.7, 138.7,
135.0, 134.0, 134.2, 129.7, 128.0, 124.6, 122.4, 120.8, 120.3, 87.8,
77.8, 74.8, 66.9, 65.8, 31.1. MS (EI) m/z 285.9 (M+, 87%), 270.9
(M+ - 15, 100%). Anal. Calcd for C20H14O2: C, 83.90; H, 4.93.
Found: C, 83.82; H, 4.93.
General Procedure for the Preparation of 4a-h. Compounds
3a-h were dissolved in dry toluene. NaOH powder was added,
and the mixture was stirred and heated under Ar for 15-60 min
with an oil-bath at 135 °C. TLC was used to monitor the end-point
of the reaction. The reaction mixture was evaporated, and the
residue was purified by column chromatography on silica. Caution:
Although no problems were experienced in the present work, care
should be taken when handling solid samples of the terminal
Acknowledgment. We thank EPSRC for funding this work.
Supporting Information Available: Description of the general
protocols for the synthesis and characterization of 3b-h and 4b-
h; copies of 1H and 13C NMR spectra of 4g and 4b; X-ray
crystallographic file for 3a, 3c, 4a, 4b, 4c, 4e, and 4f in CIF format;
additional ORTEP drawings and discussion of their structures. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JO0615697
(22) Armitage, J. B.; Entwistle, N.; Jones, E. R. H.; Whiting, M. C. J.
Chem. Soc. 1954, 147-154.
8544 J. Org. Chem., Vol. 71, No. 22, 2006