The dimer of phenylpropiolyl chloride

Article abstract of DOI:10.1016/j.tetlet.2008.01.115

Arylpropiolyl chlorides undergo dimerization to a mixture of cis- and trans-alkylidenecyclobutane-1,3-diones. The structures of these products have been established by an X-ray study of the crystalline products formed by repeated crystallization or, alternatively, by thermal gradient sublimation.

Full text of DOI:10.1016/j.tetlet.2008.01.115

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Tetrahedron Letters 49 (2008) 2049–2051
The dimer of phenylpropiolyl chloride
a,
b
c
*
Harry H. Wasserman Elga R.Wasserman , Steven J. Coats ,
Raymond E. Davis d, Vincent M. Lynch d, Kenneth B. Wiberg a
a Department of Chemistry, Yale University, New Haven, CT 06520-8108, USA
b Department of Chemistry, Harvard University, Cambridge, MA 02139, USA
c RFS Pharma, LLC, Tucker, GA 30084, USA
d Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712-0165, USA
Received 18 December 2007; revised 24 January 2008; accepted 25 January 2008
Available online 31 January 2008
Abstract
Arylpropiolyl chlorides undergo dimerization to a mixture of cis- and trans-alkylidenecyclobutane-1,3-diones. The structures of these
products have been established by an X-ray study of the crystalline products formed by repeated crystallization or, alternatively, by
thermal gradient sublimation.
Ó 2008 Elsevier Ltd. All rights reserved.
Acetylenic acid chlorides have long been known for their
high reactivity and tendency to decompose upon stor-
age.1–4 During the preparation of phenylpropiolyl chloride
from thionyl chloride and phenylpropiolic acid 1, it was
observed that distilled samples of the yellow liquid acid
chloride gradually solidified to a brick-red semi-crystalline
mass over a period of weeks.5 When this material was
recrystallized from benzene it formed beautiful deep red
crystals, mp 175–175.5 °C (45%). Elemental analysis and
molecular weight determination showed the red product
to be a dimer of phenylpropiolyl chloride, while a recent
13C NMR spectrum analysis revealed a 60–40 mixture of
two very similar compounds. An independent X-ray
crystallographic determination6 has now established the
structure of the dimer to be 2 (Scheme 1). This single crys-
tal form, obtained by slow sublimation, is quite unusual in
that the unit cell contains 3 molecules: two molecules with
the chlorine atoms ‘cis’, (Fig. 1a), and one molecule with
the chlorine atoms in the ‘trans’ configuration (Fig. 1b).
Before the availability of the NMR data, we were uncom-
fortable with our structural assignment in light of a dipole
O
Cl
Cl
O
O
O
Cl
O
and cis form
OH
Cl
DMF (cat)
>95%
1
2
Scheme 1.
moment measurement of 2.7 D7 and an earlier X-ray study
of a monoclinic crystal obtained via repeated recrystalli-
zation that contained only the ‘trans’ isomer.8 The more
recent thermal gradient sublimation also produced red
plates. A single crystal determination now shows these
plates to be a different crystal form (triclinic) consisting
solely of trans-2.6
To see if cis-2 has a dipole moment that is in accord with
the observed value for a mixture of cis- and trans-2,
calculations were carried out at the B3LYP/6-311+G* level
using the B3LYP/6-31G* geometries. As expected, the
calculated energies were similar, with cis-2 having an
energy only 0.6 kcal/mol greater than that for trans-2.
The calculated dipole moment of cis-2 was 4.09 D, in
accord with the observed value of 2.7 D for the cis/trans
mixture.
*
Corresponding author. Tel.: +1 781 538 5501.
E-mail address: harry.wasserman@yale.edu (H. H. Wasserman).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.115

2050
H. H. Wasserman et al. / Tetrahedron Letters 49 (2008) 2049–2051
O
-
Cl
a
O
O
Cl
O
Cl
O
C
Cl
+
C
OH
O
C
DMF (cat.)
>95%
O
+
1
C
C
C
O
O
[2+2]
Cl
Cl
Cl
3
2
Scheme 2.
of phenylpropiolyl chloride. Free radical traps such as
BHT and free radical initiators (AIBN, benzoyl peroxide,
and t-butyl peroxide) had no effect on the rate of dimer
formation. In addition, acids (BF3ÁEt2O, AlCl3, H2SO4,
and HCl) as well as light and moisture all failed to increase
the rate of dimer 2 formation. On the other hand, heat
accelerates the dimerization significantly, and most impor-
tantly, the dimer only forms in good yield with neat
samples of highly pure acid chloride (or DMF catalysis).
These observations have led us to propose a ben-
zylidineketene intermediate 3, which can be formed with
the participation of the aromatic ring (Scheme 2). Rapid
[2+2] cycloaddition of 3 provides 2 directly. In support
of this pathway is the more facile dimerization of p-meth-
oxypropiolyl chloride and our failure to observe any of this
reaction mode with p-nitrophenylpropiolyl chloride. In
addition, no [2+2] dimerization was observed with propiol-
yl chloride, trimethylsilylpropiolyl chloride or butaniolyl
chloride.
b
Fig. 1. (a) View of cis-2 in the mixed crystal, showing the atom labeling
scheme. Displacement ellipsoids are scaled to the 50% probability level. (b)
View of trans-2 in the mixed crystal showing the atom labeling scheme.
Displacement ellipsoids are scaled to the 50% probability level. The
molecule lies around a crystallographic inversion center at À1/2, 0, 0.
Atoms with labels appended by A are related by À1 À x, Ày, Àz.
We have found that phenylpropiolyl chloride prepared
with oxalyl chloride is particularly prone to dimerization,
and distillation can lead to an uncontrolled reaction.
From our experience, thionyl chloride is a better choice
for the preparation of distilled arylpropiolyl chlorides.
Near quantitative yield of dimer 2 can easily be obtained
in days without distillation by the reaction of oxalyl
chloride and a catalytic amount of dimethylformamide
with phenylpropiolic acid followed by solvent removal
(Supplementary data).
Crombie, et al.,9 have examined the reaction of some
phenylpropiolic acids bearing electron-releasing groups
such as 3,4-methylenedioxy, 3,4,5-trimethoxy, and 3,4-
dimethoxy with oxalyl chloride in benzene at reflux. This
reaction took a different course, yielding a chloro-
arylidenetetrahydrofuran-2,4,5-trione, 5 (Scheme 3). They
have proposed that the reaction involves the cyclization
of an intermediate mixed anhydride with oxalyl chloride
under conditions that are quite different from those in the
present work. The fact that the formation of 5 is not
observed in our work may be due to the powerful catalytic
The possibility that the reaction might be free radical in
nature was considered when, on one occasion, dimerization
took place with almost explosive force during redistillation
O
+
Cl
H
Cl-
R
Cl
O O
O
H
O
N
Cl
+
N
Cl
O
O
O
OH
O
rt
benzene
reflux
Cl-
rt
R
R
1
benzene
reflux
O
Cl
O
O
O
O
Cl
H
N
+
O
R
R
4
5
Scheme 3.

H. H. Wasserman et al. / Tetrahedron Letters 49 (2008) 2049–2051
2051
activity of DMF, which does not favor the formation of
an oxalyl chloride-mixed anhydride intermediate.
References and notes
A
1. Michael, A.; Bucher, J. E. J. Am. Chem. Soc. 1898, 20, 89; Michael,
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3. Sudborough, J. J.; Thompson, K. J. J. Chem. Soc. 1903, 83, 1153;
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4. Crombie, L.; Havard, R. G.; Reynolds, D. P. J. Chem. Soc. Chem.
Comm. 1973, 265.
control reaction, in which phenylpropiolic acid 1 was
treated with oxalyl chloride in refluxing benzene by the
method of Crombie, et. al.,9 turned reddish yellow during
the 2 h reflux. However, 13C NMR analysis of the crude
reaction mixture revealed no evidence for the formation
of dimer 2. This difference in reactivity may be explained
by the reaction of DMF with oxalyl chloride to form
the intermediate N,N-dimethylchloromethylenammonium
chloride. This product10 converts phenylpropiolic acid 1
to the acid chloride, 4 at room temperature thus eliminat-
ing the higher energy pathway to 5. The acid chloride 4
is subsequently converted to dimer 2 as previously
described in Scheme 3.
5. Wasserman, E. R., Ph.D. Dissertation, Harvard University (1949)
with Professor R. B. Woodward who supervised her dissertation
(1945–1949).
6. A summary of the crystallographic data may be found in Supple-
mentary data.
7. We thank Professor J. D. Roberts for the dipole moment
measurement.
8. Davis, Raymond E., unpublished results, 1967. Monoclinic, C2/c)
No. 15), Z = 4 in a cell of dimensions a = 19.311, b = 4.791, c =
15.801, b = 96.55.
Acknowledgment
We thank Dr. Jonathan Parr for help in preparing this
manuscript.
9. Begley, M. J.; Crombie, L.; Havard, R. G.; Reynolds, D. P. J. Chem.
Soc., Perkin Trans. 1 1976, 138; Crombie, L.; Reynolds, D. P. J.
Chem. Soc., Perkin Trans. 1 1977, 146.
10. Bohme, H.; Viehe, H. G. Iminium Salts in Organic Chemistry. In
Advances in Organic Chemistry; Taylor, E. C., Ed.; John Wiley &
Sons: New York, 1976, 1979; Vol. 9, Part 1 and Part 2.
Supplementary data
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/j.tetlet.
2008.01.115.