1-Haloalkynes from propiolic acids: A novel catalytic halodecarboxylation protocol

Full text of DOI:10.1021/jo990434g

6896
J . Org. Chem. 1999, 64, 6896-6897
Sch em e 1
1-Ha loa lk yn es fr om P r op iolic Acid s: A
Novel Ca ta lytic Ha lod eca r boxyla tion
P r otocol
Dinabandhu Naskar and Sujit Roy*
Metallo-Organic Laboratory, Inorganic Division, Indian
Institute of Chemical Technology, Hyderabad 500007, India
Received March 10, 1999
1-Haloalkynes are versatile intermediates in organic
synthesis, the design of molecular materials,1,2 and the
preparation of biocidal agents.3 Major synthetic routes4
to 1-haloalkynes to date include (a) halogenation of metal
acetylides or surrogates,5 (b) dehydrohalogenation of 1,1-
dihaloolefins,6 and (c) oxidative halogenation of terminal
alkynes.7 A synthetically new entry envisaged by us was
the halodecarboxylation of propiolic acid.
Ta ble 1. TBATF A-Ca ta lyzed Ha lod eca r boxyla tion of
R-CtC-CO2H (1) to R-CtC-X (2) w ith
N-Ha losu ccin im id e
X ) I
X ) Br
entry
R
time (h) yield (%) time (h) yield (%)
a
b
c
d
e
f
g
h
i
Ph
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
99
95
85
97
92
86
97
67
84
0.5
0.25
0.25
1
0.5
1
78
62
53
96
41
41
31
4-Me-C6H4
4-OMe-C6H4
4-Cl-C6H4
piperonyl
9-anthracenyl
1-naphthyl
2-furyl
Berliner and co-workers found that aqueous bromination
of phenylpropiolic acid afforded 11-18% of 1-bromophen-
yl acetylene among other products.8 Further oxidative
decarboxylation of phenylpropiolic acid with I2/I2O5 in
methanol/chloroform, with a 10:1:5 ratio of acid:I2:I2O5,
gave 1-iodophenyl acetylene and 2,2-diiodo-1-methoxy-
ethynyl benzene in 73% and 27% yields, respectively.9
However, the conversion was poor (<30%).
0.5
2-thienyl
Sch em e 2
In light of the above, a strategy for the efficient
transformation of phenylpropiolic acids to 1-haloacety-
lenes would be attractive. We delineate here a facile and
bench-friendly protocol for the halodecarboxylation of
propiolic acids containing aromatic or heteroaromatic
groups, under the catalytic influence of tetrabutylam-
monium trifluoroacetate, TBATFA (Scheme 1).
The reaction of phenylpropiolic acid (1 mM) with
N-iodosuccinimide (1.12 mM) and TBATFA (10 mol %)
at ambient temperature was clean and complete in 0.25
h (TLC), leading to 1-iodophenylacetylene in 99% isolated
yields (Table 1, entry a). The reaction has been extended
to various ring-substituted phenylpropiolic acids (entries
* Corresponding address: Chemistry Department, Indian Institute
of Technology, Kharagpur 721302, India.
(1) (a) Hofmeister, H.; Annen, K.; Lauren, H.; Wiechert, R. Angew.
Chem., Int. Ed. Engl. 1984, 23, 727. (b) Shair, M. D.; Yoon, T.;
Danishefsky, J . S. J . Org. Chem. 1994, 59, 3755.
(2) (a) Ratovelomanana, V.; Rollin, Y.; Gebehenne, C.; Gosmini, C.;
Perichon, J . Tetrahedron Lett. 1994, 35, 4777 and references therein.
(b) Kwock, E. W.; Bird, T., J r.; Miller, T. M. Macromolecules 1993, 26,
2935.
(3) J effery, T. J . Chem. Soc., Chem. Commun. 1988, 909 and
references therein.
(4) For reviews see: (a) Spargo, P. L. Contemp. Org. Synth. 1994,
1, 113. (b) Marsden, S. P. Contemp. Org. Synth. 1996, 133. (c) Spargo,
P. L. Contemp. Org. Synth. 1995, 85. (d) Rousseau, G.; Brunel Y.
Tetrahedron Lett. 1995, 36, 2619 and references therein.
(5) Periasamy, M.; Rao, M. L. N. Synth. Commun. 1995, 25, 2295.
(b) Ochiai, M. J . Am. Chem. Soc. 1993, 115, 2528. (c) Wagner, A.; Heitz,
A.; Mioskowski, C. Tetrahedron Lett. 1990, 31, 3141.
(6) Grandjean, D.; Pale, P.; Chuche, J . Tetrahedron Lett. 1994, 35,
3529.
b-e) and naphthyl, anthracenyl, furyl, and thienyl pro-
piolic acids (entries f-i). As can be seen from Table 1,
except in the case of 2-furyl derivative (entry h), the
yields of 1-iodoacetylenes are excellent to quantitative.
The related bromodecarboxylation reactions of acid 1
with N-bromosuccinimide and catalytic TBATFA have
been carried out successfully, giving rise to moderate to
good yields of 1-bromoacetylenes (Table 1). Additionally,
acids having enyne and bisalkyne functionalities (Scheme
2) gave the corresponding acetylenic halides 3 and 4 in
poor to good yields. In control experiments, reaction of
phenylpropiolic acid with N-bromosuccinimide in the
absence of catalyst afforded <10% of the product. In
sharp contrast, treatment of phenylpropiolic acids with
N-chlorosuccinimide, under the present conditions, leads
to total recovery of starting materials.
(7) (a) Correia, J . J . Org. Chem. 1992, 57, 4555. (b) Kulinski, T.;
J onczyk, A. Synthesis 1992, 757.
(8) (a) Ehrlich, S. J .; Berliner E. J . Am. Chem. Soc. 1978, 100, 1525.
(b) For iododecarboxylation reaction of the silver salt of phenylpropiolic
acid see: Wieland, H.; Fischer, F. G. Ann. 1926, 446, 49.
(9) Cohen M. J .; McNelis, E. J . Org. Chem. 1984, 49, 515.
On th e Mech a n ism of Ha lod eca r boxyla tion . Be-
cause the reaction was found to be unaffected in the
presence of a nitrone radical trap, we believe that the
10.1021/jo990434g CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/10/1999

Notes
J . Org. Chem., Vol. 64, No. 18, 1999 6897
Sch em e 3
halodecarboxylation proceeds by a ionic pathway. The
pathways proposed here (Scheme 3) are based on earlier
studies8 and semiempirical (AM1) calculations carried out
by us. AM1 calculations are carried out primarily to
examine the geometry around πCtC in various intermedi-
ate species and the energetics (∆Hf, heat of formation)
associated with them. For simplicity in calculation,
ammoniumtetrafluoroacetate is preferred instead of TBAT-
FA.
The pronounced catalytic effect of TBATFA suggests
that the propiolate anion halodecarboxylates faster than
acid. Because experiments are conducted in organic
solvents, the anion is likely held as a tight-ion pair with
tetrabutylammonium cation (I in Scheme 3). The HOMO
of I, at an energy of -8.78 eV, shows higher orbital
amplitude at the alkyne R-carbon (bound to carboxylate)
compared to the â-carbon (bound to phenyl ring). The
charge at the R-carbon is calculated to be -0.13 eV,
compared to -0.12 eV at the â-carbon. The above
observation strengthens the common notion that the
incoming electrophile will preferentially attack the R-car-
bon of the πCtC bond.
F igu r e 1. AM1-derived cumulative heats of formation of
plausible species (refer to Scheme 3) in the bromodecarboxy-
lation of phenylpropiolic acids. Speces A: 1 + NH4+CF3COO-
+ NBS. Species B: I + CF3COOH + NBS. Species C: III +
CF3COO- + succinimide. Species D: 2 + CO2 + NH4+CF3COO-
+ succinimide. Tetrabutylammonium ion in intermediates I
and III is substituted by ammonium ion for simplicity in
calculation.
making the halodecarboxylation route amenable to pro-
piolic acids bearing alkyl substituents.
The plausibility of the formation of intermediates II,
III, and IV has been analyzed. Stereoelectronically,
intermediate III having an open-vinyl cation will be
preferred over the weakly halo-bridging intermediate II
or carboxylate-bridged intermediate IV. The heat of
formation values (∆Hf, kcal/mole) calculated for the
intermediate II (159.23), III (159.20), and IV (157.74) are
nearly similar. Thus, it is difficult to exclude one or the
other on the basis of energetics alone. The minimized
geometries of all of the intermediates show an expected
increase in CR-Câ bond length and a concomitant in-
crease in CR-COO bond length with respect to I. The
calculated changes in heat of formation values in going
from reactants to products are shown in Figure 1, taking
the open-vinyl cation intermediate III as an example.
Although entropy parameters need to be included to get
a more clear free-energy profile of the reaction, Figure 1
provides a visualization useful in explaining the facile
nature of the present halodecarboxylation reaction.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Ha lod eca r boxyla tion of
P r op iolic Acid s. Propiolic acid 1 (1 mM) was added to a
solution of TBATFA (0.1 mM) in 3 mL of dichloroethane. After
the mixture was stirred for
5 min at room temperature,
N-halosuccinimide (1.12 mM) was added in portions. The
progress of the reaction was monitored by TLC (eluent, n-
hexane). After completion of the reaction, solvent was removed
under reduced pressure, and the mixture was subjected to
column chromatography (silica gel; eluent, n-hexane) to afford
1-haloalkynes.
Ack n ow led gm en t. Financial support to S.R. from
the Department of Science & Technology and Council
of Scientific & Industrial Research (Young Scientist
Award grant) is gratefully acknowledged. D.N. thanks
CSIR for the award of a senior research fellowship. This
is IICT communication 4250.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure, product characterization data, AM1 derived optimized
structures, orbital energy diagram and heat of formation
values of intermediates. This material is available free of
charge via the Internet at http://pubs.acs.org.
In conclusion, we have developed a synthetically at-
tractive protocol for the transformation of propiolic acids
to 1-halopropynes using readily available reagents. Cur-
rent investigations in our laboratory are focused on
J O990434G