Solvent-dependent photochemistry of 2,2,2-tribromoethyl-(2′- phenylacetate)

Article abstract of DOI:10.1021/jo301816z

Photolysis (254 nm) of the title compound 1 produces a variety of stable products, which vary significantly with the nature of the solvent. Solvents that serve as efficient H atom donors (methanol, ethanol, isopropyl alcohol) favor products arising from a net reduction of one or more of the C-Br bonds. These include 2,2-dibromoethyl-(2′-phenylacetate) 2 and 2-bromoethyl-(2′- phenylacetate) 3. In the presence of nucleophiles, products such as 2-(2′-phenylacetoxy)acetic acid 5a and/or its ester derivatives are produced. Phenylacetic acid 6 is formed in some cases but under the conditions studied appears to be a minor product. The results are interpreted in terms of a general mechanism that features formation of an iso-tribromo intermediate 9 and/or a geminate radical-atom pair.

Full text of DOI:10.1021/jo301816z

Article
pubs.acs.org/joc
Solvent-Dependent Photochemistry of 2,2,2-Tribromoethyl-(2′-
phenylacetate)
Derek M. Denning and Daniel E. Falvey*
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States
S
* Supporting Information
ABSTRACT: Photolysis (254 nm) of the title compound 1
produces a variety of stable products, which vary significantly
with the nature of the solvent. Solvents that serve as efficient H
atom donors (methanol, ethanol, isopropyl alcohol) favor
products arising from a net reduction of one or more of the
C−Br bonds. These include 2,2-dibromoethyl-(2′-phenyl-
acetate) 2 and 2-bromoethyl-(2′-phenylacetate) 3. In the
presence of nucleophiles, products such as 2-(2′-
phenylacetoxy)acetic acid 5a and/or its ester derivatives are produced. Phenylacetic acid 6 is formed in some cases but
under the conditions studied appears to be a minor product. The results are interpreted in terms of a general mechanism that
features formation of an iso-tribromo intermediate 9 and/or a geminate radical-atom pair.
escape. In the case of bromides, the general trend was to
observe mixtures of products resulting from radical as well as
cation formation.17−21
INTRODUCTION
■
The photochemistry of organohalogen compounds has
attracted much interest over the years. Halogenated com-
pounds have been used in refrigerants, flame retardants,
pesticides, and other products.1−3 Concerns about the
environmental fates of such compounds has motivated many
mechanistic photochemical studies designed to identify
environmental degradation pathways for such compounds.
Organohalides have also been studied for use as free radical
photoinitiators4 as well as photoacid generators.5−7 Finally,
there is fundamental interest in understanding the factors that
affect homolytic versus heterolytic scission of C−X bonds in
the excited state.8−12
The current work focuses on the direct photochemical
decomposition of the 2,2,2-tribromoethoxy group. This func-
tional group has been used as an electrolytically removable
protecting group for carboxylic acids, alcohols, amines, and
thiols.13−16 We have had a longstanding interest in identifying
protecting groups that can be removed via photoinduced
electron transfer. However, the current study focuses on the
direct photochemistry of the 2,2,2-tribromoethoxy group. The
behavior of this group under conditions of photoinduced
electron transfer will be described in a subsequent report.
There appear to be few, if any, experimental studies on the
photochemistry of the 2,2,2-tribromoethoxy group in particular.
However, two areas of research into related species are relevant.
First, Kropp and others examined product distributions from
the solution photolysis of various alkyl monohalides. In general,
it was concluded that the initial event is C−X bond homolysis.
For alkyl iodides in polar protic solvents, it is possible to
observe solvolysis products that result from nucleophilic
trapping of the corresponding carbenium ion. These products
were attributed to an electron transfer process in the geminal
radical pair, which in favorable cases predominates over cage
Recent time-resolved studies on the photolysis of geminal di-
and tribromides have identified an additional intermediate: the
so-called isodi(or tri)-bromomethyl species, wherein one
halogen atom dissociates from the carbon atom and reattaches
to a remaining halogen. This iso species forms within a few
picoseconds of photolysis and decays on a subnanosecond time
scale via three competing pathways: homolytic dissociation to
form radical species, addition of solvent nucleophiles to form
products of OH bond insertion, and reversion to the starting di-
or trihalide species.22−27
Experiments described below show that, unlike the
monobromo species, photolysis of 2,2,2-tribromoethyl-(2′-
phenylacetate) 1 can provide clean products that strongly
depend on the solvent. In CH3CN/H2O mixtures, photolysis
results in clean formation of a product of hydrolysis. In
contrast, when good H atom donors are employed, photolysis
produces excellent yields of mono- and didehalogenation
products. A mechanism incorporating reversible formation of
an iso-trihalo intermediate, competing homolysis, and
nucleophilic displacement reactions is proposed.
RESULTS AND DISCUSSION
■
The title compound 1 was prepared by coupling 2,2,2-
tribromoethanol and phenylacetyl chloride using standard
esterification methods as outlined in Scheme 1.28 The resulting
ester shows a maximum absorption in the UV at 210 nm along
with a shoulder or tail that, at high concentrations, extends
Special Issue: Howard Zimmerman Memorial Issue
Received: September 10, 2012
© XXXX American Chemical Society
A
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Scheme 1. Synthesis of 1
above 300 nm. These can be attributed to a superposition of
the n−σ* absorption related to the C−Br bond (ca. 210 nm)
and the typical absorption bands of the phenyl chromophore.
The compound shows little, if any, fluorescence. Attempts to
detect fluorescence from 1 (CH3CN λex = 254 nm) resulted in
negligible signals, lower in comparison to the fluorescence
quantum yield of benzene (Φ = 0.05),29 that did not differ
significantly from background.
Ester 1 was dissolved in various solvents and subjected to
254 nm photolysis, and the product distributions were
determined by 1H NMR analysis of the crude photolysis
mixtures. In most cases, product identities were further
confirmed by GC−MS analysis. The latter method, being
much more sensitive, could also detect trace products whose
Figure 1. Major products observed in the photolyses of 1 in various
solvents.
product does form, but we have not been able to identify
conditions where it is the exclusive product from 254 nm direct
photolysis.
1
yields were too low to be determined by H NMR. These are
also indicated in Table 1. Products 1, 2, and 3 have not been
previously reported, and limited characterization data can be
found on 5a and 5b, the methylated analogue of 5a, so these
species were either independently synthesized or purified from
the photolysis mixtures. Full characterization data are available
in the Supporting Information. The results of the photolysis
studies are summarized in Table 1 (see also Figure 1).
It was expected that direct photolysis of ester 1 would result
in homolytic C−Br bond fragmentation providing a radical
atom pair that could either escape the initial solvent cage and
form radical products or else form the isotribromo intermediate
9. Studies of similar species suggest that the latter would either
react with hydroxylic nucleophiles to form products of OH
bond insertion or isomerize back to form the starting material.
The dibromo alkyl radical 10 could form a variety of coupling,
H atom abstraction, and/or disproportionation products. There
is a specific interest in the possibility that this radical might
expel a carboxylate ion by way of β-bond scission leading to
formation of phenylacetic acid 6.30−32 Such a pathway would be
useful in the further development of photoreleasable protecting
groups. As will be apparent from the discussion below, this
Acetonitrile, being both polar and relatively non-nucleophilic,
was expected to optimize formation of radical 7 (Scheme 3)
(any isotribromo intermediate would presumably revert back to
starting material in the absence of a nucleophile) and
subsequent elimination to form phenylacetic acid 6 (Scheme
3 (a)). It was therefore somewhat surprising that the photolysis
of 1 in this solvent generates primarily 2-(2′-phenylacetoxy)-
acetic acid 5a with only minor amounts of the radical product
phenylacetic acid 6.
We hypothesized that the major product from these
photolyses, 5a, was the result of trapping the isohalo
intermediate 9 by trace amounts of water in the acetonitrile
solvent (Scheme 2), while the minor product, 6, could be
construed as resulting from heterolysis of the initially formed
radical 8. Reid et al. have argued, on the basis of computational
+
studies, that an ion-pair (RCBr2 ···Br−) resonance structure is a
significant contributor for 9 in the condensed phase and that H-
bonding solvents such as water should help stabilize this
species.27 This is certainly consistent with our observations of
significant products formed via 9 when water and other H-
bonding species (see below) are added. Adding water to the
Table 1. Product Ratios from Photolysis of 1 in Various Solvents
entry
solvent
[1] (mM)
time (min)
1
2
3
4
5a−e
31.2 a
6
T1
MeCN
MeCN
MeCN
MeOH
MeOH
15.13
15.13
15.13
15.88
15.88
20.12
27.61
13.80
22.70
19.87
16.50
13.47
18.54
18.96
60
120
180
30
61.7
26.9
10.2
61.0
3.7
59.9
23.3
8.6
0
7.1
T2
62.4 a
75.1 a
16.6 b
27.9 b
40.1 a
76.7 b
71.4 a
10.7
14.7
T3
T4
22.4
T5
60
44.9
a
a
23.5
20.0
T6
MeCN-d3
90
T7
MeOH-d4
90
T8
MeCN (16.7% H2O)
ethanol
60
b
b
a
T9
60
a
(<45)
88
55
12
c
a
T10
T11
T12
T13
T14
2-propanol
60
0
a
d
a
a
tert-butyl alcohol
cyclohexane
60
4.9
0
a
48.7 a, e
46.4
60
c
THF (no BHT)
THF (with BHT)
60
0
c
d
30
0
(<100)
a
b
c
Minor amounts of this product were detected by GC−MS. Based on reported chemical shifts.33 Only product identified by 1H NMR
d
1
accompanied by numerous unidentified major products. Major product identified by H NMR accompanied by numerous unidentified minor
products.
B
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Scheme 2. Proposed Mechanism for the Solvent Trapping of Isohalo Intermediate 9
Scheme 3. Proposed Reaction Pathways for the Observed Photolysis Products of 1
acetonitrile increased the rate of conversion but did not
significantly affect the yield of phenylacetic acid 6. The H
our observation that the photochemical conversion rate
increases when water is added to the acetonitrile. For example,
60 min of photolysis in nominally dry acetonitrile converts
<40% of the starting material compared to >90% in acetonitrile
with 17% water (entries T1 and T8 in Table 1). It is interesting
that the ratio of phenylacetic acid 6 to 5a is not significantly
affected upon addition of water. This observation implies that
the heterolysis step leading to the formation of phenylacetic
acid 6 (step f) is also promoted by the addition of water. The
latter effect is presumably due to water increasing the polarity
of the solvent and thus accelerating the heterolytic bond
cleavage (pathway d) to approximately the same extent it
accelerates the nucleophilic trapping of 9 leading to 5a
(pathway e).
Also notable is the solvent isotope effect when comparable
runs were carried out in CD3CN (entry T6 in Table 1). In this
case only 5a can be detected in the photolysis mixture, and the
homolysis/elimination product 6 falls below the limit of
detection. This can be attributed to a kinetic isotope effect on
the trapping of the Br atom in the geminate radical pair 8. The
latter can either recombine to form the isotribromo
intermediate 9 or, if free radicals are formed through cage
escape or H atom transfer to the Br atom, through elimination
of phenylacetate ion. The deuterated solvent is slower to trap
the Br atom, resulting in fewer free radicals and thus low (<5%)
yields of 6.
1
NMR spectrum of the unpurified photolysis mixture indicates
that the two products form cleanly with negligible byproducts
(entries T1−T3 in Table 1). Indeed in our hands, this
photochemical route proved to be a more practical method for
generating isolable quantities of 2-(2′-phenylacetoxy)acetic acid
than a previously published procedure.34
The latter results are consistent with the mechanism shown
in Scheme 3. Excited state homolysis provides a geminate
radical pair and the latter partitions between recombination to
form the isotrihalo intermediate 9 and cage escape (reversibly)
forming a free dibromoalkyl radical and bromine atom. The
isotrihalo intermediate either combines with water, eventually
forming 2-(2′-phenylacetoxy)acetic acid 5a, or isomerizes back
to form the reactants. Phenylacetic acid could form through a
secondary heterolysis of the dibromoalkyl radical 8, although
given the low yields of this product, it is apparently not a
particularly fast process relative to competing reactions such as
radical recombination and H atom abstraction (which will be
described subsequently). While recent ultrafast spectroscopic
studies on related systems cause us to favor 9 as the key
intermediate, the alternative pathway wherein electron transfer
would form a carbenium ion intermediate as suggested by
Kropp et al. (pathway c in Scheme 3) cannot be excluded on
the basis of the data from the current study.
The competition between nucleophlic trapping (pathway d)
Photolysis in methanol provides two significant products: a
and reversion to starting material (pathway e) is supported by
monodebrominated product 2 and a substitution product 5b
C
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(entries T4 and T5 in Table 1). The major product 2 results
from a net reduction of the C−Br bond. This presumably arises
through H atom transfer from the solvent to the intermediate
dibromoalkyl radical 8. Unlike in CH3CN, where this radical
eliminates the phenylacetoxy ion, radical 8 is apparently able to
abstract a H atom from the solvent. While CH3CN and
CH3OH have similar bond dissociation energies (96.0 and 96.1
kcal/mol, respectively)35 previous work has shown that
electron-poor radicals similar to 8 react more rapidly with
electron-rich C−H bonds in substrates such as CH3OH
compared with electron-deficient C−H bonds in substrates
such as CH3CN.36,37 This mechanism is supported by a
significant kinetic isotope effect. The use of CD3OD suppresses
formation of reduction product 2, and the substitution product,
found to be phenylacetic acid and 2-(2′-phenylacetoxy)acetic
(entry T11 in Table 1). It would appear that the tert-butyl
alcohol is too sterically hindered to allow for efficient trapping
of the isohalo intermediate, conceding to the addition of trace
amounts of water. The formation of 4 under these conditions
was also confirmed by mass spectrometry.
In solvents that are less polar and non-nucleophilic, such as
cyclohexane and THF, the singly reduced species 2 is the only
1
product that can be detected in the H NMR of the crude
photolysis mixture. However, these photolyses were not clean.
The spectra showed that numerous unidentified minor
products also accompanied 2. However none were individually
formed in sufficient yield to permit complete characterization.
In contrast, when photolyses were carried out in THF that had
0.025% of the preservative BHT, then 2 was clearly the major
product and preparative quantities could be generated and
isolated under these conditions (entries T12−14 in Table 1).
1
5a, is the only product detected by H NMR (entry T7 in
Table 1).
The minor product in CH3OH, 5b, presumably arises from
the analogous methanol trapping of the isotrihalo intermediate
9. The resulting α,α-dibromoether would rapidly hydrolyze.
This process would lead to the formation of 5b. The identity of
5b was further confirmed by comparison to a 1H NMR
spectrum of an independently synthesized sample as well by
HPLC analysis.
Similar C−Br bond reduction is observed in ethanol, a
solvent that is a stronger H atom donor (C−H BDE = 94.8
kcal/mol).35 However, in this case, the two major products
observed were ethyl phenylacetate 4 and 2-bromoethyl-(2′-
phenylacetate) 3 (entry T9 in Table 1). These products
obviously result from multiple C−Br bond reductions. We note
that control experiments showed that 4 can also form from
(thermal) Fischer esterification of the phenylacetic acid product
6 in cases where HBr (the presumed byproduct of reduction or
substitution reactions) is added to a solution of 6 in ethanol.
Thus, there is some uncertainty as to how much of product 4
results from a Fischer esterification pathway as compared to the
sequential reduction of 1. However, as will be described below,
the formation of 4 in comparable experiments using isopropyl
alcohol as the solvent suggests that Fischer esterification of 6 is
only a small contributor to its overall yield.
CONCLUSION
■
Direct photolysis of 1 provides a variety of products that are
strongly dependent on the solvent used in the experiments.
Despite this diversity of outcomes, all of the product studies
reported here are consistent with the general mechanism
depicted in Scheme 3. An initial C−Br homolysis step creates a
radical atom pair. The latter can form an isotribromo
intermediate 9. This intermediate either reverts to starting
material or is trapped by nucleophiles to form 5a−e.
Alternatively, the radical pair 8 can either proceed through a
series of steps to form reduction products such as 2−4 or
undergo heterolysis to form elimination product 6. The ratio of
these products depends on the ability of the solvent to serve as
an H atom donor or nucleophile. Strong H atom donors favor
the reductive pathways. Indeed, with BHT it is possible to
achieve preparatively useful yields of the dibromo product 2.
Likewise when water, but no good H atom donor, is provided,
preparatively useful yields of 5a can be obtained. While 6 is
formed under many conditions, we are unable to identify
conditions where it is the major product. Our data suggest that
the challenge is competing formation of the isotribromo species
from the geminate radical pair. This provides an intermediate
that is apparently sufficiently long-lived to be trapped by trace
amounts of nucleophiles. One potential solution to this
problem would be photochemical electron transfer, which
ought to provide the desired radical 8, accompanied by the
bromide rather than a bromine atom and circumventing
formation of 9. Such an approach is the subject of our current
investigations.
It is not clear at this time why NMR-detectable amounts of
the singly reduced species 2 are not observed (trace amounts of
this product are in fact detected by GC−MS). One possibility is
that the newly formed 1-hydroxyethyl radical can further serve
as a one electron reducing agent leading to the formation of
acetaldehyde and compound 3 upon further hydrogen
abstraction.
Photolysis of 1 in 2-propanol (C−H BDE = 91.0 kcal/mol)35
provides results similar to those observed in ethanol. The
doubly debrominated compound 3 is the major component in
the photolysis mixture (entry T10 in Table 1). Presumably, the
isopropyl radical formed from the first hydrogen abstraction
can serve as a reducing agent leading to the formation of
acetone. Smaller amounts of the completely debrominated
product 4 are also detected. In this case, 4 clearly forms
through sequential C−Br bond reductions as Fischer
esterification of 6 would lead to isopropyl phenylacetate rather
than 4. The more sensitive GC−MS shows that in fact trace
amounts of the isopropyl ester do form, along with minor
amounts of substitution product 5d.
EXPERIMENTAL SECTION
■
General Experimental Conditions. All reagents were acquired
through commercial sources and used without further purification.
Solvents were used directly from commercial sources and stored in
sealed amber bottles with 4 Å molecular sieves. MeCN was distilled
from CaH2 and stored in a similar fashion as previously stated. NMR
data was collected on a 400 MHz spectrometer in CDCl3 or CD3CN
and chemical shifts (δ) are reported in ppm relative to the solvent
1
peak. H NMR spectra are reported as follows: chemical shift (ppm),
multiplicity (m, multiplet; t, triplet; d, doublet; s, singlet), integration
and coupling constants (Hz). Product purification by flash
chromatography was done using silica gel, 40−63 μm. Reactions
were monitored by GC equipped with an FID detector.
General Photolysis Procedure. Photolysis experiments were
done in a capped quartz cuvette purged with nitrogen gas for 15 and 3
min for the solution head space. Isolation reactions were carried out in
Omission of a good hydrogen donating source such as when
tert-butyl alcohol is used as the photolysis solvent, provides
results consistent with the findings of no reduction products
1
identifiable by H NMR. Instead, the major products were
D
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a capped 120 mL quartz test tube and were purged with nitrogen gas
for a minimum of 20 and 10 min for the head space. Irradiations were
conducted on an 8-bulb Rayonet reactor using 253.7 nm light bulbs.
After a certain amount of irradiation time, the photolysis mixture was
transferred to a vial, and the solvent was removed under reduced
pressure. The unpurified products were redissolved in CDCl3 and
The mixture was heated under reflux (70 5 °C) for 5 h with stirring.
The reaction mixture went from chalky white to clear upon the
duration of heating. After 5 h, the reaction was concentrated under
reduced pressure and the contents were transferred to a 125 mL
separatory funnel using 50 mL of deionized H2O. The aqueous layer
was extracted with 150 mL of diethyl ether. The organic layer was
dried over Na2SO4, filtered, and concentrated under reduced pressure
1
subjected to H NMR analysis.
1
to yield a clear watery oil (4.22 g, 91.1%). H (400 MHz, CDCl3): δ
Synthesis of 2,2,2-Tribromoethyl-(2′-phenylacetate) (1).
2,2,2-Tribromoethanol (2.00 g, 7.07 mmol), triethylamine (1.97 mL,
14.1 mmol), phenylacetyl chloride (1.87 mL, 14.1 mmol), and dry
CH2Cl2 (30 mL) were stirred at room temperature overnight. After 12
h a GC trace of the mixture confirmed consumption of the starting
material. The reaction mixture was transferred to a 125 mL separatory
funnel, and the organic layer was washed with deionized H2O (3 × 50
mL) and cold 1 M HCl (3 × 50 mL). The organic layer was dried over
MgSO4, filtered, and concentrated under reduced pressure to afford an
orange watery oil. Purification of the ester was done by flash column
chromatography with 1:1 hexanes/CH2Cl2 as eluent. The ester was
7.32 (m, 5H), 4.63 (s, 2H), 3.746 (s, 2H), 3.740 (s, 3H). 13C (400
MHz, CD3CN): δ 172.4, 169.6, 135.4, 130.7, 129.8, 128.4, 62.2, 53.1,
41.4. FT-IR (ATR): neat, 1740.97 cm−1. HRMS (ESI-TOF) m/z:
[M]+ calcd for C11H12O4 209.0814; found 209.0803.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H NMR, 13C NMR, IR, and MS spectra for all
1
synthesized and isolated compounds. H NMR spectra for the
1
obtained as a very faint peach colored watery oil (2.19 g, 77.0%). H
aforementioned photolysis reactions of 1 (Table 1). GC−MS
data and specifications for selected photolysis reactions as well
as HPLC chromatograms for confirmation of products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(400 MHz, CDCl3): δ 7.32 (m, 5H), 4.94 (s, 2H), 3.79 (s, 2H). 13C
(400 MHz, CD3CN): δ 171.3, 135.1, 131.0, 129.9, 128.6, 77.9, 41.7,
37.1. FT-IR (ATR): neat, 1748.19 cm−1. HRMS (ESI-TOF) m/z:
[M]+ calcd for C10H9Br3O2 400.8211; found 400.8214.
Isolation of 2,2-Dibromoethyl-(2′-phenylacetate) (2). Com-
pound 1 (98.3 mg, 0.245 mmol) was added to a 120 mL quartz test
tube with 30 mL of THF containing 0.025% BHT. The solution was
irradiated for 90 min, and the solvent was removed under reduced
pressure. A NMR of the crude photolysis mixture confirmed the loss of
starting material and the formation of 2. The crude product was
transferred to a 125 mL separatory funnel with 30 mL of CH2Cl2. The
organic layer was washed with deionized water (3 × 30 mL) and
saturated NaHCO3 solution (2 × 30 mL), dried over MgSO4, filtered,
and concentrated under reduced pressure. The still crude mixture by
NMR proved difficult to purify, but this was accomplished by flash
column chromatography using a gradient of 95:5, hexanes/ethyl
acetate followed by 90:10, hexanes/ethyl acetate as the eluent. Ester 2
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: falvey@umd.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Chemistry Division of the
National Science Foundation.
1
was obtained as a watery clear oil (7.70 mg, 9.75%). H NMR (400
MHz, CDCl3): δ 7.33 (m, 5H), 5.70 (t, 1H, J = 6.4 Hz), 4.58 (d, 2H, J
= 6.4 Hz), 3.71 (s, 2H) 13C (400 MHz, CD3CN): δ 171.9, 135.3,
130.9, 129.9, 128.5, 70.6, 42.0, 41.6. FT-IR (ATR): neat, 1740.82
cm−1. HRMS (ESI-TOF) m/z: [M]+ calcd for C10H10Br2O2 322.9106;
found 322.9116.
REFERENCES
■
(1) de Wit, C. A. Chemosphere 2002, 46, 583−624.
(2) Haeggblom, M. M.; Bossert, I. D. Dehalogenation 2003, 3−29.
(3) Alaee, M.; Arias, P.; Sjodin, A.; Bergman, A. Environ. Int. 2003,
29, 683−689.
(4) Monroe, B. M.; Weed, G. C. Chem. Rev. 1993, 93, 435−448.
(5) Gannon, T.; McGimpsey, W. G. J. Org. Chem. 1993, 58, 913−
916.
Isolation of 2-Bromoethyl-(2′-phenylacetate) (3). Compound
1 (73.7 mg, 0.184 mmol) was added to a 120 mL quartz test tube with
30 mL of 2-propanol. The solution was irradiated for 90 min and the
solvent was removed under reduced pressure. A NMR of the crude
photolysis mixture confirmed the loss of starting material and the
formation of 3. The crude mixture proved difficult to purify but was
accomplished by flash column chromatography using a gradient of
95:5, hexanes/ethyl acetate followed by 90:10, hexanes/ethyl acetate
as the eluent. The remaining product appeared to be a clear watery oil
(4.90 mg, 11.0%). 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 5H), 4.42
(t, 2H, J = 6.0 Hz), 3.68 (s, 2H), 3.51 (t, 2 H, J = 6.0 Hz). 13C (400
MHz, CDCl3): δ 171.3, 133.8, 129.5, 128.8, 127.4, 64.3, 41.3, 28.7. FT-
IR (ATR): neat, 1735.81 cm−1. HRMS (ESI-TOF) m/z: [M]+ calcd
for C10H11BrO2 243.0021; found 243.0033.
(6) Barra, M.; Redmond, R. W.; Allen, M. T.; Calabrese, G. S.; Sinta,
R.; Scaiano, J. C. Macromolecules 1991, 24, 4972−4977.
(7) Scaiano, J. C.; Barra, M.; Calabrese, G. S.; Sinta, R. J. Chem. Soc.,
Chem. Commun. 1992, 1418−1419.
(8) Galli, C.; Gentili, P.; Guarnieri, A.; Kobayashi, S.; Rappoport, Z. J.
Org. Chem. 1998, 63, 9292−9299.
(9) Wagner, P. J.; Sedon, J.; Waite, C.; Gudmunsdottir, A. J. Am.
Chem. Soc. 1994, 116, 10284−10285.
(10) Wender, P. A.; Jeon, R. Org. Lett. 1999, 1, 2117−2120.
(11) van Dorp, J. W. J.; Lodder, G. J. Org. Chem. 2008, 73, 5416−
5428.
Isolation of 2-(2′-Phenylacetoxy)acetic acid (5a). Compound
(12) Krijnen, E. S.; Zuilhof, H.; Lodder, G. J. Org. Chem. 1994, 59,
8139−8150.
(13) Kasafirek, E. Tetrahedron Lett. 1972, 20, 2021−2024.
(14) Semmelhack, M. F; Heinsohn, G. E. J. Am. Chem. Soc. 1972, 94,
5139−5140.
(15) Engels, J. Angew. Chem. 1979, 91, 155−156.
(16) Engels, J. Liebigs Ann. Chem. 1980, 4, 557−563.
(17) Kropp, P. J.; Poindexter, G. S.; Pienta, N. J.; Hamimlton, D. C. J.
Am. Chem. Soc. 1976, 98, 8135−8144.
(18) Kropp, P. J.; Pienta, G. S. J. Org. Chem. 1983, 48, 2084−2090.
(19) Moret, E.; Jones, C. R.; Grant, B. J. Org. Chem. 1983, 48, 2090−
2092.
1 was added to a 120 mL quartz test tube with 40 mL of acetonitrile.
1
The reaction was monitored by H NMR until the loss of starting
material could be confirmed. The solvent was removed under reduced
1
pressure, and the resulting product was characterized. H (400 MHz,
CDCl3): δ 7.32 (m, 5 H), 4.68 (s, 2H), 3.76 (s, 2H). 13C (400 MHz,
CD3CN): δ 172.3, 169.7, 135.3, 130.7, 129.7, 128.3, 61.9, 41.2. FT-IR
(ATR): CH3CN subtracted: 3235 cm−1, 1745.39 cm−1, 1655.18 cm−1.
HRMS (ESI-TOF) m/z: [M]− calcd for C10H9O4 194.0535; found
194.0503.
Synthesis of 2-Methoxy-2-oxoethyl-(2′-phenylacetate)
(5b).34 Phenylacetic acid (3.03 g, 22.2 mmol), potassium carbonate
(2.80 g, 20.2 mmol), methyl bromoacetate (2.30 mL, 24.3 mmol), and
acetone (30 mL) were added to a flask was equipped with a condenser.
(20) Kropp, P. J. Acc. Chem. Res. 1984, 17, 131−137.
E
dx.doi.org/10.1021/jo301816z | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(21) Kropp, P. J.; Adkins, R. L. J. Am. Chem. Soc. 1991, 113, 2709−
2717.
(22) Huang, H.-Y.; Chuang, W.-T.; Sharma, R. C.; Hsu, C.-Y.; Lin,
C.-H. J. Chem. Phys. 2004, 121, 5253−5260.
(23) Kwok, W. M.; Zhao, C.; Li, Y.-L.; Guan, X.; Phillips, D. L. J.
Chem. Phys. 2004, 120, 3323−3332.
(24) Kwok, W. M.; Zhao, C.; Li, Y.-L.; Guan, X.; Wang, D.; Phillip,
D. L. J. Am. Chem. Soc. 2004, 126, 3119−3131.
(25) Carrier, S. L.; Preston, T. J.; Dutta, M.; Crowther, A. C.; Crim,
F. F. J. Phys. Chem. A. 2010, 114, 1548−1555.
(26) Kalume, A.; George, L.; Reid, S. A. J. Phys. Chem. Lett. 2010, 1,
3090−3095.
(27) George, L.; Kalume, A.; Esselman, B. J.; Wagner, J.; McMahon,
R. J.; Reid, S. A. J. Chem. Phys. 2011, 135, 1245031−1245038.
(28) Perrotta, R, R.; Winter, A. H.; Falvey, D. E. Org. Lett. 2011, 13,
212−215.
(29) Dawson, W. R.; Windsor, M. W. J. Phys. Chem. 1968, 72, 3251−
3260.
(30) Tanner, D. D.; Chen, J. J.; Chen, L.; Luelo, C. J. Am. Chem. Soc.
1991, 113, 8074−8081.
(31) Sundararajan, C.; Falvey, D. E. Photochem. Photobiol. Sci. 2006,
5, 116−121.
(32) Borak, J. B.; Falvey, D. E. J. Org. Chem. 2009, 74, 3894−3899.
(33) Peng, C.; Zhang, W.; Yan, G.; Wang. J. Org. Lett. 2009, 11,
1667−1670.
(34) Ringshaw, D. J.; Smith, H. J. J. Chem. Soc. 1964, 1559−1562.
(35) Luo, Y.-R. Tabulated BDE’s of C-H Bonds: Handbook of Bond
Dissociation Energies in Organic Compounds; CRC Press: Boca Raton,
FL, 2003; pp 57, 76.
(36) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
John Wiley & Sons: Chichester, U.K.; 1985; pp 182−188.
(37) Russell, G. A. Free Radicals; Kochi, J. K., Ed.; Wiley: New York,
1973; Vol. 1; pp 293−298.
F
dx.doi.org/10.1021/jo301816z | J. Org. Chem. XXXX, XXX, XXX−XXX