Kinetic study on denomination of vic-dibromides with trivalent phosphorus compounds

Article abstract of DOI:10.1002/hc.1035

Various types of trivalent phosphorus compounds (I) brought about reductive debromination of vic-dibromides (2) to afford olefins. The reaction was accelerated by either electron-releasing substituents on the phosphorus of 1 or electron-with-drawing substituants on the α-carbon of 2. The substituent effects, along with the stereochemistry of the reaction, are consistent with an E1CB-like mechanism for the elimination of the two bromine atoms. That is, 1 initially undergoes nucleophilic attack upon a bromine of 2. At the transition state, a fractional positive charge is developed on the phosphorus of 1 and a fractional negative charge on the carbon of 2. This mechanism suggests the importance of an electronic character of the vic-dibromide in determining the relative ease of bromophilicity, carbophilicity, and basicity of the phosphorus of a trivalent phosphorus compound in a reaction with the dibromide. α 2001 John Wiley & Sons, Inc.

Full text of DOI:10.1002/hc.1035

Heteroatom Chemistry
Volume 12, Number 4, 2001
Kinetic Study on Debromination of vic-
Dibromides with Trivalent Phosphorus
Compounds
Shinro Yasui,1 Kenji Itoh,2 and Atsuyoshi Ohno2
1Tezukayama College, Gakuen-Minami, Nara, 631-8585 Japan
2Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011 Japan
Received 18 September 2000; revised 16 November 2000
4]. Meanwhile, mechanisms involving radical inter-
ABSTRACT: Various types of trivalent phosphorus
compounds (1) brought about reductive debromina-
tion of vic-dibromides (2) to afford olefins. The reac-
tion was accelerated by either electron-releasing
substituents on the phosphorus of 1 or electron-with-
drawing substituents on the ␣-carbon of 2. The sub-
stituent effects, along with the stereochemistry of the
reaction, are consistent with an E1CB-like mechanism
for the elimination of the two bromine atoms. That is,
1 initially undergoes nucleophilic attack upon a bro-
mine of 2. At the transition state, a fractional positive
charge is developed on the phosphorus of 1 and a frac-
tional negative charge on the carbon of 2. This mech-
anism suggests the importance of an electronic char-
acter of the vic-dibromide in determining the relative
ease of bromophilicity, carbophilicity, and basicity of
the phosphorus of a trivalent phosphorus compound
in a reaction with the dibromide. ᭧ 2001 John Wiley
& Sons, Inc. Heteroatom Chem 12:217–222, 2001
mediates have been proposed for debromination of
vic-dibromides with electron donors such as 1-ben-
zyl-1,4-dihydronicotinamide [5] or sodium naph-
thalenide [6]. Cathodic reduction of vic-dibromides
also results in the debromination [7].
Trivalent phosphorus compounds, which are
known to be either nucleophiles or electron donors
[8,9], have been shown to act as nucleophiles in re-
action with vic-dibromides [10–13]. Such reactivity
of these phosphorus compounds is due to their much
higher oxidation potentials compared with the re-
duction potentials of vic-dibromides. Meanwhile,
there are three possible electrophilic sites in vic-di-
bromides, upon which trivalent phosphorus com-
pounds can attack nucleophilically, namely, bro-
mine, hydrogen, or carbon. For example, triethyl
phosphite can undergo the Arbuzov reaction with
some 1,2-dibromoethanes by attacking the carbon of
the dibromide; however, the phosphite attacks the
bromine to result in debromination of vic-dibro-
mides that have electron-withdrawing groups adja-
cent to both bromine atoms [12]. Furthermore, tri-
valent phosphorus compounds can attack the
hydrogen atom of some vic-dibromides, resulting in
the elimination of HBr [13].
INTRODUCTION
vic-Dibromides are debrominated by many reagents
that exert Lewis base reactivity. For example, several
types of nucleophiles bring about debromination of
vic-dibromides by attacking a bromine of the start-
ing vic-dibromide or a bromonium intermediate [1–
A question arises as to what factors determine
the relative ease of bromophilicity, carbophilicity,
and basicity (affinity to a hydrogen) of the phospho-
rus of a given trivalent phosphorus compound. To
seek an answer to this question, we carried out the
reactions of trivalent phosphorus compounds 1a–h
Correspondence to: Shinro Yasui.
Contract Grant Sponsor: Tezukayama Research Grant (to S. Y.).
᭧ 2001 John Wiley & Sons, Inc.
217

218 Yasui, Itoh, and Ohno
SCHEME 1
TABLE 1 Debromination of 2 with Ph3P (1c)a
with vic-dibromides 2x–z. The reactions took place,
affording the products from debrominations of 2,
namely, olefins 4, along with oxidation products
from 1, namely, pentavalent oxo-compounds 3
(Scheme 1). The results from quantitative analyses
including kinetics on the reactions showed that an
initial step of each reaction is nucleophilic attack by
the phosphorus of 1 upon the bromine of 2. Based
on this mechanism, we herein discuss the relative
ease of bromophilicity, carbophilicity, and basicity
exerted by each of the trivalent phosphorus com-
pounds in reactions with the vic-dibromides.
Yield/%
2
time/min
2b
trans-4
cis-4
1c
3b
c
c
c
meso-2x
dl-2x
erythro-2y
180
240
210
13
88
6
87
5
94
12
85
6
88
5
77
aIn MeCN:MeOH (10:1 v/v) at 70ЊC under Ar in the dark. [1c] ס [2]
ס 1.00 ן 10מ2 M.
bRecovered.
cNot detected.
for the formation of dibromotriphenylphosphorane
Ph3PBr2 was obtained in these reactions.
RESULTS
The time course of the reaction of 1c with meso-
2x was examined with GC, as shown in Figure 1,
which indicated a 1:1 stoichiometry. The examina-
tion allows us to estimate roughly the second-order
Reactions of Triphenylphosphine 1c with vic-
Dibromides 2
Triphenylphosphine 1c (1.00 ן 10מ2 M) was reacted
with an equimolar amount of 2 in acetonitrile con-
taining methanol (MeCN:MeOH ס 10:1 v/v) under
an argon atmosphere. Due to the poor solubility of
meso-2x in the solvent at room temperatures, the re-
actions were carried out at an elevated temperature
(70ЊC). After an appropriate reaction period, the re-
action mixture was analyzed by gas chromatography
(GC) and gas chromatography–mass spectrometry
(GC-MS). As reported in Table 1, meso-2x and ery-
thro-2y were debrominated to give trans-4x and
trans-4y, respectively, in nearly quantitative yields,
without giving the cis-isomers. Also, dl-2x af-
forded trans-4x, but the yield was much lower. In
these reactions, 1c was converted to a theoretical
amount of triphenylphosphine oxide 3c. No evidence
מ2
rate constant k2 of this reaction to be 6 ן 10
M
מ1sמ1. In Figure 1 are shown theoretical curves
based on this value of k2, along with experimental
data points.
Kinetics
For the reactions of 1a–h with 2z, kinetics investi-
gations were carried out at 25ЊC under pseudo-first-
order conditions in which 1 was present in large ex-
cess. The progress of each reaction was followed by
monitoring the increase in the absorbance at 351 nm
of the olefin 4z, which gave pseudo-first-order rate
constants with correlation coefficients Ͼ 0.999. With
experiments with different concentrations of 1, the

Kinetic Study on Debromination of vic-Dibromides with Trivalent Phosphorus Compounds 219
TABLE 2 Rate Constants for the Reaction of 1 with meso-
4-nitro-stylbene dibromide (meso-2z) in the Presence of
MeOHa
מ1
1
k2/Mמ1 s
Eopx/Vb
1a
1b
1c
1d
1e
1f
1.38 ן 10
1.20
0.36
0.82
0.94
1.20
1.24
1.50
1.52
1.90
מ1
מ1
מ1
מ2
מ3
מ4
1.71 ן 10
1.65 ן 10
1.10 ן 10
2.98 ן 10
5.77 ן 10
1.24 ן 10
1g
1h
aIn MeCN at 25ЊC under Ar in the dark. [1] ס (ϳ1.0–6.0) ן 10מ3 M,
[meso-2z] ס 5.0 ן 10מ5 M, [MeOH] ס 0.1 M.
ם
bPeak oxidation potential vs Ag/Ag .
bromonium mechanism is well known [2,4]. How-
ever, this is not the case, as shown in Table 1, thus
eliminating further consideration of this mechanism
for the present reaction. In addition, we can hardly
imagine what could cause initial elimination of a
bromide ion to form the bromonium intermediate.
Trivalent phosphorus compounds that have a P–
O–C linkage, phosphite 1h, phosphonites 1f,g, and
phosphinites 1d,e could undergo the Arbuzov reac-
tion with 2, in which case an initial step would be
nucleophilic attack by 1 upon the carbon bonded to
the bromine. Any possibility of such a reaction can
be discarded, however, because there is no evidence
for formation of the Arbuzov product. In addition,
linearity in the log k2 מ Eopx correlation shown in
Figure 2 (vide infra) suggests strongly that the re-
actions of 1a–h proceed according to a single mech-
anism; of these phosphorus compounds, phosphines
1a–c cannot undergo the Arbuzov reaction in
principle.
To elucidate further the mechanism, we here ex-
amine the results of kinetics investigations on the
debromination of 2z with 1a–h. In Figure 2, the log-
arithm of k2 (Table 2) is plotted against peak oxida-
tion potential Eopx of 1, a quantity that evaluates elec-
tronic effects of ligands on the phosphorus of 1.
Indeed, we have shown that Eopx values of trivalent
phosphorus compounds Z3P with open-chain struc-
tures (the compounds examined in this article) cor-
relate linearly with the sum of the Taft’s substituent
constants r* of the ligands Z, Rr*, with the slope
DEopx/DRr* ס 0.35 [14]. That is, the plot in Figure 2
is equivalent to a Taft plot. There is a good linear
correlation between log k2 and Eopx (correlation co-
efficient r ס 0.96), with the slope being מ3.0. This
value of the slope is converted to a reaction constant
q*, defined by an equation log k2 ס q*Rr* ם const.,
FIGURE 1 Time-course for the reaction of 1c with meso-2x.
Closed triangles and open triangles represent 1c and 3c re-
spectively. Open circles and closed circles represent meso-
2x and trans-4, respectively. Dashed lines are theoretical
ones; see the text.
second-order rate constant k2 was obtained for each
reaction, as summarized in Table 2.
DISCUSSION
vic-Dibromides undergo reductive debromination
either by nucleophilic attack by nucleophiles [1–4]
or through the single electron transfer (SET) mech-
anism [5–7]. Although trivalent phosphorus com-
pounds can act sometimes as electron donors [8],
peak oxidation potentials of 1 (ranging from 1 to 2
ם
V vs. Ag/Ag ) [14] are much higher than peak reduc-
tion potentials of 2 (determined by cyclic voltam-
ם
metry; מ2.14 V, מ2.07, and מ1.49 V vs. Ag/Ag for
meso-2x, erythro-2y, and erythro-2z, respectively),
predicting that the SET from 1 to 2 would be highly
endothermic if it were to occur. Besides, use of an
oxygen atmosphere was found to exhibit no effect on
the yields of the debromination products. Therefore,
the debromination of 2 with 1 observed here cannot
be explained by an SET mechanism, but 1 acts as a
nucleophile in the present reactions.
With this premise, we first examined a possibility
of a bromonium mechanism as depicted in the lower
part of Scheme 2. That is, 2 initially releases a bro-
mide ion to form a bromonium cation intermediate,
which is followed by nucleophilic attack by 1 upon
the resulting intermediate to afford the product 4.
This mechanism predicts the formation of cis-4x
from dl-2x because complete stereospecificity in a

220 Yasui, Itoh, and Ohno
SCHEME 2
meso-2z, is debrominated by 1c with k2 ס 1.71 ן
10מ1 Mמ1 sמ1 at 25ЊC (Table 2). On the other hand, it
has been roughly estimated that the debromination
of the unsubstituted derivative, meso-2x, with 1c
takes place with k2 ס 6 ן 10מ2 Mמ1sמ1 at 70ЊC. Since
these k2 values have been obtained for different tem-
peratures and we have no data concerning activation
parameters, direct comparison of these constants is
impossible. However, clearly a 4-nitro-substituent in
a meso-stilbene dibromide accelerates its debromi-
nation significantly; meso-2z is debrominated three
times faster than the unsubstituted derivative, meso-
2x, even at a temperature of 35Њ lower. This obser-
vation indicates a significant amount of a negative
charge developed on the carbon at the transition
state.
With the results previously stated in mind, we
propose an E1CB-like mechanism for the debromi-
nation of 2 with 1. As depicted in the upper part of
Scheme 2, the phosphorus of 1 undergoes initial nu-
cleophilic attack upon the bromine atom of 2 to give
a carbanion-like intermediate (or a transition state),
from which the second bromine is being eliminated
as a bromide ion. At the transition state of this pro-
cess, charge separation occurs, and fractional posi-
tive and negative charges are developed on the phos-
phorus of 1 and the carbon of 2, respectively.
Consistent with this mechanism is the observed stoi-
chiometry, 1:2 ס 1:1. Furthermore, as expected from
FIGURE 2 Plot of log k2 vs Epox for the reactions of 1a–h with
meso-2x.
by using the relationship between Eopx and Rr*. Thus,
q* ס מ1.1 is obtained, which clearly shows that a
positive charge is developed largely on the phospho-
rus at the transition state of the debromination of 2z
with 1 [15].
meso-4-Nitro-substituted stilbene dibromide,

Kinetic Study on Debromination of vic-Dibromides with Trivalent Phosphorus Compounds 221
this mechanism, meso-2x and erythro-2y give trans-
indeed reflected in the lower yield of trans-4 from dl-
2x (Table 1).
4 in high yields. Thus, anti-elimination of two bro-
mines from a meso- (or erythro-) isomer takes place
easily to give the trans-olefin because the anti con-
formation with respect to the two bromines is ther-
modynamically the most stable one for the meso- (or
erythro-) isomer (Scheme 3).
Emphasized here again is that the bromine atom
in 2x–z is preferred, irrespective of the configuration
of 2, over the hydrogen atom or the carbon atom as
the site of nucleophilic attack by the phosphorus of
1. The affinity of the phosphorus to the bromine may
not be surprising when one takes into account the
hard and soft acids and bases (HSAB) principle [17];
trivalent phosphorus compounds are soft bases, and
a bromine is softer than a hydrogen or a carbon.
However, such an argument is an oversimplification.
Surveying literature presented so far, we find that,
when treated with vic-dibromides, trivalent phos-
phorus compounds sometimes undergo reactions
that are not predictable by the HSAB principle. In a
series of reactions of triethyl phosphite 1h with 1,2-
dibromoethane derivatives, 1h undergoes the Arbu-
zov reaction with unsubstituted 1,2-dibromoethane
by attacking the carbon of this dibromide, whereas
1h attacks the bromine when the 1,2-dibromoethane
bears an electron-withdrawing substituent on the ␣-
carbon [12]. This fact suggests that the bromine is
preferred in nucleophilic attack by the phosphorus
only when a carbanion center resulting from re-
moval of the bromine is sufficiently stabilized. Also
against prediction by the HSAB principle is the re-
For the dl-isomer, on the other hand, a confor-
mation in which a bromine and a hydrogen are lo-
cated at anti positions with respect to each other is
the relatively highly stable (or possibly the most
stable) one (Scheme 3). From this conformation,
anti-elimination of HBr would be more favorable in
energy than syn-elimination of two bromines. Nev-
ertheless, dl-2x is in fact debrominated in reaction
with 1c to afford trans-4, although the yield is low,
without giving a product resulting from HBr elimi-
nation (Table 1). This fact suggests strongly that nu-
cleophilic attack by 1c on the bromine of dl-2x is also
the initial step in this case. The resulting carbanion-
like intermediate from this isomer is transformed to
a less crowded conformer, from which the second
bromine is eliminated as a bromide ion to afford
trans-4. Such syn-elimination would require more
energy than the anti-elimination; that is, debromi-
nation from the dl-isomer would be more sluggish
than that from the meso- (or erythro-) isomer. This is
SCHEME 3

222 Yasui, Itoh, and Ohno
action of triphenylphosphine 1c with erythro-2,3-di-
bromobutyric acid, which results in elimination of
HBr instead of elimination of two bromine atoms;
the phosphorus of 1c initially attacks the hydrogen
of the vic-dibromide [13]. High acidity of the ␣-hy-
drogen due to the electronegative carboxyl group
certainly accounts for this result.
Kinetics
Into a UV-vis quartz cell equipped with a silicon
rubber stopper and filled with argon gas were added
successively the solution of 1 in acetonitrile, the so-
lution of meso-2z in acetonitrile, and methanol. The
stock solutions of 1 and of meso-2z had been pre-
pared under an argon atmosphere, with adjustment
of their concentrations such that the concentrations
of 1, meso-2z, and methanol became (ϳ1.0–6.0) ן
10מ1 M, 5.0 ן 10מ5 M, and 0.1 M, respectively, after
the mixing. Increase in the absorbance at 351 nm
resulting from formation of trans-4z was followed on
a spectrophotometer.
These facts now allow us to conclude that an
electronic character of a given vic-dibromide mainly
determines the relative ease of bromophilicity, car-
bophilicity, and basicity exerted by the phosphorus
of a trivalent phosphorus compound in a reaction
with the dibromide. With increasing electronegativ-
ity of substituents on the carbon bonded to the bro-
mine in a vic-dibromide, the bromine becomes more
amenable to attack by the phosphorus; in other
words, the bromophilicity of the phosphorus be-
comes higher. Introduction of electronegative sub-
stituents on the carbon bonded to the bromine atom
also enhances the apparent carbophilicity of the
phosphorus as well, but the influence of such sub-
stituents is larger in enhancing the bromophilicity
[18]. The present work has revealed that bromophil-
icity of the phosphorus atom in trivalent phosphorus
compounds is well exerted toward vic-dibromides 2
that bear phenyl and/or ethoxycarbonyl groups on
the ␣-carbon. This reactivity of 2 results from a sub-
tle balance in electronegativity effects of substituents
of 2. If the dibromide has less powerful electroneg-
ative substituents, the carbon would be preferred in
nucleophilic attack by the phosphorus of 1. On the
other hand, if the substituents are highly electroneg-
ative, the ␣-hydrogen becomes so acidic that it would
be easily removed by attack by the phosphorus
reagent.
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EXPERIMENTAL
Instruments
Gas chromatography analysis was accomplished
with a Shimadzu GC-14B gas chromatograph. Mass
spectra were obtained on a Shimadzu GCMS-
QP2000A gas chromatograph–mass spectrometer
equipped with a Shimadzu GC-MSPAC 200S data
processor. UV-visible spectra were recorded on a Hi-
tachi U-3212 spectrophotometer.
[14] Yasui, S.; Tsujimoto, M.; Okamura, M.; Ohno, A. Bull
Chem Soc Jpn 1998, 71, 927–932.
[15] Debromination of 2z with tris (2,6-dimethoxy-
phenyl)phosphine 1a takes place undoubtedly
through a nucleophilic mechanism because 1a is an
efficient nucleophile but a poor electron donor [16].
Therefore, the fact that the point for the reaction with
1a fits the linear line given in Figure 2 confirms the
nucleophilic mechanism occurring in the debromi-
nation also with other phosphorus compounds 1b–h.
[16] Yasui, S.; Tsujimoto, M.; Itoh, K.; Ohno, A. J Org
Chem 2000, 65, 4715–4720.
[17] Ho, T.-L. Hard and Soft Acids and Bases Principle in
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Materials
Trivalent phosphorus compounds (1a–h) and vic-di-
bromides (2x,y) were commercially available (Tokyo
Chemical Industry). erythro-1,2-Dibromo-1-(4Ј-ni-
trophenyl)-2-phenylethane (2z) was prepared by the
reaction of 4-nitrostilbene with pyridinium tribrom-
ide in dichloromethane at room temperature (86%
yield).