Synthesis of 1-[4-(3-chlorobenzoyl)phenyl]-2-phenylacetylene

Full text of DOI:10.1080/00304948.2011.582010

This article was downloaded by: [The University of Manchester Library]
On: 08 October 2014, At: 09:59
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Organic Preparations and Procedures
International: The New Journal for
Organic Synthesis
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/uopp20
Synthesis of 1-[4-(3-
Chlorobenzoyl)phenyl]-2-
phenylacetylene
Matthew C. Davis a & Thomas J. Groshens a
a Chemistry & Materials Division, Michelson Laboratory , Naval Air
Warfare Center , China Lake, California, 93555, USA
Published online: 09 Jun 2011.
To cite this article: Matthew C. Davis & Thomas J. Groshens (2011) Synthesis of 1-[4-(3-
Chlorobenzoyl)phenyl]-2-phenylacetylene, Organic Preparations and Procedures International: The
New Journal for Organic Synthesis, 43:3, 314-318
To link to this article: http://dx.doi.org/10.1080/00304948.2011.582010
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Organic Preparations and Procedures International, 43:314–318, 2011
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.582010
Synthesis of
1-[4-(3-Chlorobenzoyl)phenyl]-2-phenylacetylene
Matthew C. Davis and Thomas J. Groshens
Chemistry & Materials Division, Michelson Laboratory, Naval Air Warfare
Center, China Lake, California 93555, USA
The contemporary synthetic approach to a molecule containing a 1,2-diarylacetylene moiety
is through the Sonogashira reaction, a transition metal-catalyzed reaction of an arylacety-
lene with an aryl halide.1,2 Although this reaction is typically high yielding, there can
be problems with removal of residual catalyst and associated phosphine-ligands from the
product.3 Strategies for purification become ever more significant when the scale of synthe-
sis increases and distillation, sublimation, and chromatography become costly and and time
consuming. The present study was a brief exploration into the possibility of synthesizing a 1-
aroylphenyl-2-phenylacetylene by dehydrohalogenation4–9 rather than palladium-catalyzed
processes.10,11
The structure of 1-[4-(3-chlorobenzoyl)phenyl]-2-phenylacetylene (4) is shown in
Scheme 1. Attempts to simply acylate 1,2-diphenylacetylene under Friedel-Crafts con-
ditions following a patent report12 were failures. The acetylene group is highly reactive and
requires protection such as a cobalt coordination complex for this method to be viable.13
Similar failures resulted in attempts to acylate trans-stilbene.
A classical method to prepare 1,2-diphenylacetylene is by the double dehydrobromina-
tion of stilbene dibromide (1,2-dibromo-1,2-diphenylethane), a prototypical undergraduate
laboratory experiment.14 Stilbene dibromide is most often prepared by bromination6 of
stilbene but can also be synthesized from bibenzyl (1) by bromination with bromine or
N-bromosuccinimide (NBS). If bibenzyl could be acylated once,15 then this route to 4
might be applicable.
Friedel-Crafts acylation of 1 with less than one equivalent of 3-chlorobenzoyl chloride
gave the desired benzophenone 2 in 59% yield. Unfortunately, all attempts to purify 2 from
the diacylated by-product by recrystallization were unsuccessful as both products appeared
to co-crystallize; silica gel chromatography was necessary to separate them. Reaction of
2 following conditions of Green, Remers and Wilson16 (NBS, carbon tetrachloride, 2,2ꢀ-
azobisisobutyronitrile) gave the diastereomerically pure dibromide 3 in nearly quantitative
This article not subject to U.S. copyright law.
Submitted August 20, 2010.
Address correspondence to Matthew C. Davis Chemistry & Materials Division, Michelson Lab-
oratory, Naval Air Warfare Center, China Lake, CA 93555, USA. E-mail: matthew.davis@navy.mil
314

Synthesis of 1-[4-(3-Chlorobenzoyl)phenyl]-2-phenylacetylene
315
Scheme 1
yield. A pair of doublets is observed in its 1H NMR for the methine protons with a coupling
constant of 11.5 hertz which is typical of an anti conformation of vicinal hydrogens.17 The
erythro configuration of 3 was confirmed by single-crystal X-ray analysis (Figure 1). The
BrCCBr torsion angle of 175◦ is similar to several other X-ray structures18–22 of compounds
containing a meso 1,2-dihalo-1,2-diarylethane.
Initial attempts to dehydrobrominate 3 to 4 using the traditional conditions14 of excess
potassium hydroxide in boiling ethylene glycol gave no product, althoug none of the start-
ing material was recovered. Milder conditions (tetrahydrofuran, two equivalents potassium
tert-butoxide, 0◦C)23 accomplished this reaction very smoothly and led to a nearly quanti-
tative formation of 4. Simple pouring of the reaction mixture into water precipitated 4 as an
analytically pure white solid. Single-crystal X-ray analysis confirmed the structure of the
Figure 1
Crystal Structures of Compounds 3 and 4.

316
Davis and Groshens
final product. It appears that potassium tert-butoxide/THF is an ideal base/solvent in these
eliminations since even meso-stilbene dibromide gave 1,2-diphenylacetylene nearly quanti-
tatively at room temperature. In summary, a novel route to 1-[4-(3-chlorobenzoyl)phenyl]-
2-phenylacetylene in 3-steps from bibenzyl is described with an overall yield of 55%.
Experimental Section
The melting points were obtained on a Mel-Temp II from Laboratory Devices (Holliston,
MA) and are uncorrected. All NMR data were collected on a Bruker Avance II 300 MHz
spectrometer (1H at 300 MHz, 13C at 75 MHz). Nuclear magnetic resonance data (free-
induction decay’s) were determined using NUTS software from Acorn NMR (Livermore,
CA). All spectra are referenced to CDCl3 or TMS. The bibenzyl (1), 3-chlorobenzoyl
chloride and all reagents were purchased from Sigma-Aldrich (Milwaukee) and used as
received. Elemental analyses were performed by Atlantic Microlab, Inc. (Norcross, GA).
1-[4-(3-Chlorobenzoyl)phenyl]-2-phenylethane (2)
A 250 mL round-bottomed flask equipped with magnetic stirring bar was charged with
10.74 g (59 mmol) of 1 and 6.85 g 3-chlorobenzoyl chloride (39 mmol). The mixture
was gently heated to dissolve all the solids. With vigorous mixing, 5.19 g (39 mmol) of
AlCl3 was added portionwise over 20 min. The mixture became warm and copious HCl gas
was evolved (HOOD). After the addition, the mixture was heated at 60◦C for 1 h. Water
(250 mL) was carefully added to quench the reaction. After being cooled to rt, the mixture
was extracted twice with 100 mL portions of Et2O. The organic extracts were combined
and washed with 100 mL H2O followed by 100 mL saturated aqueous Na2CO3 and finally
100 mL brine. After drying over anhydrous MgSO4, the solvent was evaporated in vacuo
leaving 15.29 g of a crude white solid. The solid was chromatographed on silica gel
(10% Et2O in hexanes) to give 7.42 g (59%) of the title compound. Recrystallization from
heptane gave the title compound as colorless needles, mp. 73–75◦C.
1H NMR (CDCl3): δ 7.75 (t, J = 2.3 Hz, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.64 (dt,
J = 7.9 and 1.1 Hz, 1H), 7.54 (dm, J = 8.2 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.33–7.24
(m, 4H), 7.23–7.12 (m, 3H), 2.98 (m, 4H); 13C NMR (CDCl3): δ 195.09, 147.54, 141.27,
139.82, 134.98, 134.72, 132.32, 130.51, 130.01, 129.78, 128.81, 128.63, 128.17, 126.36,
38.07, 37.59.
Anal. Calcd for C21H17ClO: C, 78.62; H, 5.34. Found: C, 78.53; H, 5.30.
The doubly acylated product 1,2-bis[4-(3-chlorobenzoyl)phenyl]ethane (2.1 g, 30%) was
also isolated as colorless needles from HOAc, mp. 174–177◦C.
1H NMR (CDCl3): δ 77.76 (t, J = 1.9 Hz, 2H), 7.74 (d, J = 8.3 Hz, 4H), 7.65 (dt,
J = 7.8 and 1.6 Hz, 2H), 7.56 (dm, J = 8.3 Hz, 2H), 7.42 (t, J = 7.8 Hz, 2H), 7.29 (d, J =
8.3 Hz, 4H), 3.07 (s, 4H); 13C NMR (CDCl3): δ 195.09, 146.79, 139.72, 135.24, 134.77,
132.42, 130.61, 130.04, 129.83, 128.81, 128.19, 37.55.
Anal. Calcd for C28H20Cl2O2: C, 73.21; H, 4.39. Found: C, 73.39; H, 4.37..
erythro 1,2-Dibromo-1-[4-(3-chlorobenzoyl)phenyl]-2-phenylethane (3)
A 250 mL round-bottomed flask equipped with magnetic stirring bar and reflux con-
denser was charged with 4.48 g (14 mmol) of 2, 6.23 g (35 mmol), of NBS 70 mg

Synthesis of 1-[4-(3-Chlorobenzoyl)phenyl]-2-phenylacetylene
317
2,2ꢀ-azobisisobutyronitrile and 50 mL CCl4. The mixture was refluxed for 1 h after which
time the reaction was complete as shown by silica thin-layer chromatography. The reaction
mixture was partitioned between 200 mL EtOAc and 200 mL H2O. The organic phase was
separated and washed with 100 mL saturated aqueous Na2SO3 and then 100 mL brine.
After drying over anhydrous MgSO4, the solvent was evaporated in vacuo leaving 6.6 g
(98%) of a white solid. Recrystallization from i-PrOH gave the title compound as white
needles, mp. 168–170◦C.
1H NMR (CDCl3): δ 7.85 (d, J = 8.3 Hz, 2H), 7.81 (t, J = 2.0 Hz, 1H), 7.69 (dt,
J = 7.7 and 1.4 Hz, 1H), 7.64 (d, J = 8.3 Hz, 2H), 7.59 (dm, J = 7.7 Hz, 1H), 7.55–7.49
(m, 2H), 7.48–7.34 (m, 4H), 5.53 (d, Jab = 11.5 Hz, 1H), 5.47 (d, Jab = 11.5 Hz, 1H); 13
C
NMR (CDCl3): δ 194.56, 144.96, 139.73, 139.27, 137.46, 134.97, 132.78, 130.73, 130.05,
129.96, 129.45, 129.10, 128.36, 128.32, 128.18, 55.59, 54.99.
Anal. Calcd for C21H15Br2ClO: C, 52.70; H, 3.16. Found: C, 53.23; H, 3.02.
1-[4-(3-Chlorobenzoyl)phenyl]-2-phenylacetylene (4)
A 100 mL round-bottomed flask equipped with magnetic stirring bar was charged with
700 mg (6.2 mmol) of KOtBu and 25 mL of anhydrous THF. The mixture was cooled in
an ice bath and a solution of 1.5 g (3.1 mmol) of 3 in 10 mL anhydrous THF was added
dropwise over 5 min. After the addition, the cooling bath was removed and the mixture
was stirred at rt for 1 h. Addition of 25 mL H2O precipitated a white solid which was
collected on a medium porosity glass frit and air-dried (940 mg, 96%). Recrystallization
from EtOH/dimethoxyethane gave the title compound as colorless rods, mp. 153–155◦C.
1H NMR (CDCl3): δ 7.81–7.73 (m, 3H), 7.68–7.59 (m, 3H), 7.59 (m, 3H), 7.43 (d,
J = 7.6 Hz, 1H), 7.39–7.32 (m, 3H); 13C NMR (CDCl3): δ 194.99, 139.29, 136.24, 134.85,
132.59, 131.96, 131.74, 130.19, 129.98, 129.87, 129.04, 128.64, 128.25, 128.15, 122.82,
93.09, 88.77.
Anal. Calcd for C21H13ClO: C, 79.62; H, 4.14. Found: C, 79.66; H, 4.06.
1,2-Diphenylacetylene
A 100 mL round-bottomed flask equipped with magnetic stirring bar was charged with
2.23 g meso stilbene dibromide (6.55 mmol) and 200 mL anhydrous THF under N2. After
allowing all the solids to dissolve, 1.62 g KOtBu (14.4 mmol) was added and the mixture
was stirred at rt for 30 min. It was then poured into 200 mL H2O and extracted with
100 mL Et2O twice. The extracts were combined and washed with brine and then dried
over anhydrous MgSO4. Evaporation in vacuo gave 1.12 g (96%) of the title compound as
a colorless crystalline solid, mp. 58–60◦C, lit.14 59–61◦C.
Anal. Calcd for C14H10: C, 94.34; H, 5.66. Found: C, 94.35; H, 5.65.
X-ray Structure Determination of 3 and 4
CCDC 784621 (3) and CCDC 784620 (4) contain the supplementary crystallographic data
which can be obtained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif, by e-mailing data request@ccdc.cam.ac.uk, or
by contacting CCDC 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

318
Davis and Groshens
Acknowledgements
This work was supported by an In-house Laboratory Independent Research award from
the Office of Naval Research. Thanks to Ann M. Moorehead of the Technical Library for
collecting reference 15.
References
1. K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 16, 4467 (1975).
2. R. Chinchilla and C. Na´jera, Chem. Rev., 107, 874 (2007).
3. C. J. Welch, J. Albaneze-Walker, W. R. Leonard, M. Biba, J. DaSilva, D. Henderson, B. Laing,
D. J. Mathre, S. Spencer, X. Bu and T. Wang, Org. Process Res. Dev., 9, 198 (2005).
4. P. Pfeiffer, Z. Phys. Chem., 48, 40 (1904).
5. A. C. Cope and S. W. Fenton, J. Am. Chem. Soc., 73, 1668 (1951).
6. L. I. Smith and M. M. Falkof, ‘Organic Syntheses’, Coll. Vol. 3, p. 350, Wiley, New York, NY,
1955.
7. H. N. C. Wong, P. J. Garratt and F. Sondheimer, J. Am. Chem. Soc., 96, 5604 (1974).
8. S. Chaffins, M. Brettreich and F. Wudl, Synthesis, 1191 (2002).
9. A. Orita and J. Otera, Chem. Rev., 106, 5387 (2006).
10. A. Furstner and G. Seidel, Tetrahedron, 51, 11165 (1995).
11. R. Rathore, C. L. Burns and S. A. Abdelwahed, Org. Lett., 6, 1689 (2004).
12. K. S. Y. Lau, T.-A. Chen, B. A. Korolev, E. Brouk, P. E. Schilling and H. W. Thompson, US
Patent 6,124,421, 26 September 2000; Chem. Abstr., 131, P32511g (1999).
13. D. Seyferth and A. T. Wehman, J. Am. Chem. Soc., 92, 5520 (1970).
14. L. F. Fieser, J. Chem. Educ., 31, 291 (1954).
15. M. Farcasiu and C. Smith, Energy & Fuels, 5, 83 (1991).
16. F. D. Greene, W. A. Remers and J. W. Wilson, J. Am. Chem. Soc., 79, 1416 (1957).
17. I. G. Pojarlieff, P. M. Ivanov and N. D. Berova, J. Mol. Struct.: THEOCHEM, 91, 283 (1983).
18. I. Ya. Postovskii, V. A. Zyryanov, V. L. Rusinov, N. A. Klyuev, G. G. Aleksandrov, A. I.
Chernyshev and S. E. Esipov, Chem. Hetercycl. Compd., 19, 454 (1983).
19. A. N. Chekhlov, S. A. Lermontov, S. I. Zavorin and N. S. Zefirov, Dokl. Akad. Nauk., 323, 77
(1992).
20. R. Alarco`n, O. Cox, L. A. Rivera and S. D. Huang, Acta Cryst., C54, 68 (1998).
21. D. O’Hagan, H. S. Rzepa, M. Schu¨ler and A. M. Z. Slawin, Beilstein J. Org. Chem., 2, (2006),
doi:10.1186/1860-5397-2-19.
22. B. R. Bhogala and A. Nangia, New J. Chem., 32, 800 (2008).
23. C. F. Wilcox Jr. and K. A. Weber, J. Org. Chem., 51, 1088 (1986).