Photo-Fries rearrangement of aryl acetamides: Regioselectivity induced by the aqueous micellar green environment

Article abstract of DOI:10.1039/c5pp00349k

Photochemical reactions tend to give more than one photoproduct. However, such a reaction can be a powerful synthetic tool when it is possible to conduct it in regioselective conditions yielding a single photoproduct. Water-surfactant solutions as reaction media can be considered as an approach in this context because they show products with different features than those from isotropic solutions. Here we describe results obtained from studying the effect on the prototypical photoreaction, known as the photo-Fries reaction of several substituted acetanilides and α-naphthyl acetamide within surfactant micelles (ionic and non-ionic micelles). This reaction involves homolytic cleavage of a C-N bond to yield a singlet radical pair. The surfactant micelles control the rotational and translational mobility of the radical pair, resulting in noticeable photoproduct selectivity.

Full text of DOI:10.1039/c5pp00349k

View Article Online
View Journal
Photochemical &
Photobiological
Sciences
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Iguchi, R. Erra-
Balsells and S. M. Bonesi, Photochem. Photobiol. Sci., 2015, DOI: 10.1039/C5PP00349K.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/pps

Page 1 of 22
Photochemical & Photobiological Sciences
Photo-Fries rearrangement of aryl acetamides: regioselectivity induced by the aqueous
View Article Online
DOI: 10.1039/C5PP00349K
micellar green environment.
Daniela Iguchi, Rosa Erra-Balsells and Sergio M. Bonesi*
CIHIDECAR – CONICET, Departamento de Química Orgánica, FCEyN, University of Buenos
Aires, Pabellón 2, 3er Piso, Ciudad Universitaria, 1428, Buenos Aires, Argentina. Fax: +54-11-
4576-3346; Tel: +54-11-4576-3346; E-mail: smbonesi@qo.fcen.uba.ar
Abstract. Photochemical reactions tend to give more than one photoproduct. However, such
reactions can be a powerful synthetic tool when is possible to conduct it in regioselective conditions
yielding a single photoproduct. Water – surfactant solutions as reaction media can be considered as
an approach in this context because show products feature different than those from isotropic
solutions. Here we describe results obtained studying the effect on the prototypical photoreaction,
known as the photo-Fries reaction of several substituted acetanilides and -naphthyl acetamide
within surfactant micelles (ionic and non-ionic micelles). This reaction involves homolytic cleavage
of a C – N bond to yield a singlet radical pair. The surfactant micelles control the rotational and
translational mobility of the radical pair, resulting in noticeable photoproduct selectivity.
Introduction.
Generally, photochemical reactions tend to give more than one product. For such reactions to be
useful in synthesis it is necessary to be able to control the experimental conditions to yield a single
product. Therefore, product selectivity in reactions goes on as a great challenge in synthetic organic
photochemistry, especially when radical pairs or radical–ion pairs are formed as primary
intermediate species. The use of confined assemblies, such as zeolites, micelles, polyolefin films,
cavitands, dendrimers, etc., can be considered as devising strategies to control product distributions
in photochemical reactions.1 The restricted mobility within the hydrophobic cores of these confined
assemblies limits the tendency of radicals, radical cations, or other reactive intermediates to
undergo radical–destroying bimolecular reactions and prevents the access to adventitious reagents
(i.e. water and oxygen) that would cause their decay in solution. In the present article we describe
the results of our studies on the use of cationic, anionic and neutral surfactant micelles, which are
capable of solubilizing organic molecules (hydrophobic molecules) in water, as the media in
achieving product selectivity in the prototypical photoreaction, the photo-Fries reactions of several
substituted aryl acetanilides.
The photo-Fries rearrangement reaction was discovered by Anderson and Reese2 and
involves the homolytic cleavage of a carbon–heteroatom bond, i.e., C-O, C-S and C-N, of esters,

Photochemical & Photobiological Sciences
Page 2 of 22
thioesters and amides, respectively.3 The radical mechanism of the photo-Fries rearrangement is
View Article Online
DOI: 10.1039/C5PP00349K
well established and it is known that this rearrangement occurs mainly through the excited singlet
state.1i,4 Previous studies on the product distribution of the photo-Fries rearrangement reaction of
(hetero)aryl amides in isotropic media afforded ortho- and para-rearranged photoproducts as well
as the corresponding aryl amine (Scheme 1).5
O
NH2
NH2 O
NH2
HN
R'
h
R'
+
+
Solvent
25ºC
R
O
R
R
R
R'
Scheme 1. The photo-Fries rearrangement of acetanilides.
Surfactants, which are amphiphilic molecules, aggregate in solution to form micelles when
its concentration is above the critical micellar concentration (cmc). Under this condition, the
micelles enhance solubility of hydrophobic compounds in water. In fact, the most important
property of micelles is that they have the ability to concentrate guest molecules into relatively small
effective volumes and then to promote the re-encounter of such molecules.1c,6 The model of a
micelle usually presented is such that the interior contains the hydrophobic chain part of the
amphiphilic moiety while the polar head group (charge or neutral head) are located at the surface,
forming a double layer in contact with the surrounding water. Micelles are not static species but
rather exist in a dynamic equilibrium with the surfactant monomers, they can be employed to
organize organic substrates.7 In micelles, large cage effects are observed relative to homogeneous
solvents whose magnitude cannot be explained by the microviscosity inside the micelle. The main
reason for this observation is that the hydrophobicity of the solutes inhibits diffusion into the
aqueous phase, thereby increasing the time spent by the reaction intermediates in the restricted
space of the micelle. If the intermediates are geminate radical pairs, which are produced
photochemically, rotational and translational mobility of these species are constrained inside the
micelles. Therefore, the product distribution and the relative chemical yield of the products
observed in micellar solution can be significantly different relative to homogeneous solution.1m,7
There has been a lot of studies on controlling the reactivity of radicals generated within the
micelle supercage where polarity, viscosity, electrostatic, and hydrophobic interactions as well as
hydrogen-bonding solvation may play critical roles in determining their reactivities.8 In addition,
several studies directed to analyze and quantify micellar cage effects (reactivity, selectivity and
efficiency) on photochemical reactions in water have been performed. Because the photo-Fries
rearrangement involves in-cage recombination versus diffusion of radicals, aryl esters have been

Page 3 of 22
Photochemical & Photobiological Sciences
chosen as model substrates to study the nonhomogeneous environments.9 In these studies, SDS was
View Article Online
DOI: 10.1039/C5PP00349K
also the preferred surfactant among other ionic surfactants for carry out the photoreactions.
However, some examples in the literature show that the photo-Fries rearrangement reaction of
benzamides in SDS micellar solution and acetanilides in water - cyclodextrin systems has been also
studied.9f-g Since 2-amino arylketones are key synthons in the preparation of 4-quinolones and their
derivatives, with demonstrated biological and pharmaceutical properties,10 we decided to study the
photo-Fries rearrangement of a series of substituted aryl and polycyclic aryl amides in micellar
solution in order to evaluate if provides high selectivity for 2-amino phenones formation within the
micelle assembly. The structures of the aryl acetamides and surfactants employed in this study are
shown in Scheme 2.
(a) Structures of aryl amides.
O
O
O
O
O
HN
HN
HN
1; R = H
HN
R
HN
2; R = CH3
3; R = OCH3
4; R = OPh
5; R = Cl
6; R = CN
7; R = COCH3
8; R = NO2
R1
R2
OCH3
OCH3
11; R2 = CH3
12; R2 = Cl
13; R2 = NO2
15
9; R1 = CH3
10; R1 = Cl
14
(b) Structures of surfactants.
Cationic Surfactants.
Cetyl trimethyl ammonium bromide (CTAB)
Br
Cl
N
N
cmc: 0.92 mM
Cetyl trimethyl ammonium chloride (CTAC)
cmc: 1.25 mM
Anionic Surfactant.
Sodium dodecyl sulfate (SDS)
cmc: 8.2 mM
Na
O
O
O
O
S
Non-ionic Surfactants.
Polyoxyethylene(22)lauryl ether (Brij P35)
OH
cmc: 0.09 mM
O
O
22
O
O
OH
Polyoxyethylene octyl phenyl ether (Triton-X-100)
cmc: 0.3 mM
8-9
Scheme 2. Structures of the aryl acetamides and the surfactants studied.
Experimental.
Materials and equipment. Acetanilide, ortho-, meta and para-substituted anilines, 3,4-
dimethoxyaniline and -naphthylacetamide were purchased from Aldrich and were used without

Photochemical & Photobiological Sciences
Page 4 of 22
further purification. Surfactants (SDS, Brij, CTAC, CTAB, Triton X-100 and Tween 80) were
View Article Online
DOI: 10.1039/C5PP00349K
purchased from Fluka and Sigma Aldrich. Spectrograde solvents were obtained from J. T. Baker
and were used as received. Pyridine was distilled and stored over KOH pellets. Melting Points were
1
determined on a Fisher Jones apparatus and are not corrected. H and 13C NMR spectra were
registered on a Bruker AC-200 spectrometer in CDCl3; chemical shifts ( are reported in part per
million (ppm), relative to internal tetramethylsilane. 2D NOESY spectra were registred on a Bruker
AC-500 spectrometer in D2O; chemical shifts ( are reported in part per million (ppm), relative to
internal trimethylsilylpropionic acid. Coupling constant (J) values are given in Hz. The
measurements were carried out using the standard pulse sequences. GC analysis was carried out on
a Hewlett Packard 5890 gas chromatograph using an Ultra 2 capillary chromatographic column. For
amides 1 – 14, the chromatograms were recorded with the following program: initial temperature:
100 ºC, 2 minutes; rate: 10 ºC.min-1; final temperature: 250 ºC, 10 minutes. For amide 15, the
chromatograms were recorded as follows: initial temperature: 150 ºC, 2 minutes; rate: 10 ºC.min-1;
final temperature: 250 ºC, 15 minutes. Reverse phase HPLC analysis was carried out on a JASCO
PU 1580 with a UV detector PU 1575 using a RP – 18 reverse chromatographic column (Supelco;
eluent: MeCN – H2O mixtures; flow: 1 mL.min-1; detector: UV,  230 and 260 nm). The UV-
visible spectra were measured with a Shimadzu UV-1203 spectrophotometer. All the measurements
were made with 1 cm stoppered quartz cells at 298 K.
Determination of the constants of binding (Kb) of acetanilides in micellar media. Solutions of
acetanilides 4, 11, 12 and 13 were prepared in deionized water (MilliQ) and their concentration
varied between 5.5x10-5 M and 1.0x10-4 M. An aliquot (2 mL) of the acetanilide solution was placed
in a two-faced stoppered quartz cuvette provided with a stir bar and the UV-visible spectrum was
registered, then the A0 value at the maximum wavelength was read. Next, aliquots of concentrated
surfactant solution (10 L) were added successively and the UV-visible spectra were registered
taking for each solution the A value at the maximum wavelength. After each addition of surfactant
solution the resulting solution was stirred during 20 minutes. With the values of A0 and A in hands,
plots of (A0/(A - A0) versus the reciprocal of the concentration of the surfactants were carried out
and the data were fitted with a linear regression program provided by SigmaPlot version 11.0. From
the ratio of the slope and the origin it was easily to calculate the Kb values.
Synthesis of acetanilides 2 – 15. To a solution of the acetanilides (0.010 mol) in pyridine (10 mL)
chilled in an ice-bath were added dropwise acetyl chloride (0.012 mol) during 10 minutes under
stirring. The reaction mixture was standing for additional 45 minutes under stirring. Once tlc
confirmed total consumption of the starting material, the reaction mixture was extracted with
dichloromethane (10 mL) and washed with a solution of diluted HCl (10 mL). The organic phase
was then washed with water, dried with Na2SO4, filtrated and evaporated under pressure. The

Page 5 of 22
Photochemical & Photobiological Sciences
acetanilides were purified from the solid residue by column chromatography with hexane and ethyl
View Article Online
DOI: 10.1039/C5PP00349K
acetate mixtures giving the corresponding acetanilides in excellent yields ( 90 %). The acetanilides
2 – 14 were characterized by comparison of physical constant (m.p.) and spectroscopical data (1H-
NMR and 13C-NMR) reported in the literature. These data and the corresponding references are
listed in Electronic Supplementary Information section.
Photoirradiations. General procedure. Photoirradiations of acetanilides in homogeneous media.
Stock solutions of amides 1 – 15 (0.106 mmol) in cyclohexane (100 mL) were prepared. An aliquot
(65 mL) was placed in a stoppered Erlenmeyer quartz flask (100 mL) and degassed with argon for
30 min. The flask was placed in a home made optical bench provided with the possibility to use two
or four lamps. The solutions of the amides were stirred during the irradiation process. Irradiations
with λexc = 313 nm were carried out with four phosphorous – coated lamps (HelioQuartz, each of 18
Watts, purchased in Italy) that give a nearly parallel beam at 313 nm. Irradiations with λexc = 254
nm were carried with four germicide lamps (Philips, each of 20 Watts, purchased in Argentina). The
progress of the reaction was monitored by TLC [eluent: hexane–ethyl acetate (8 : 2 v/v); spots were
visualized with UV light (254 and 366 nm) and with I2] and by GC analysis (Ultra 2 capillary
column) following the programs above mentioned depending on the amide analyzed. When the
conversion of the starting material was higher than 90%, the photolyzed solution was evaporated
carefully to dryness under reduced pressure. The yellowish solid residue obtained was worked up
by silica gel column chromatography (eluent: hexane 100% followed by hexane–ethyl acetate
mixtures). From the eluted fractions, the photoproducts were isolated and characterized by mean of
physical and spectroscopic methods.
Photoirradiations of acetanilides in micellar media. Stock solutions of surfactants in deionized
water were freshly prepared and the concentrations of these solutions were: SDS 0.10 M; CTAC
0.02 M; CTAB 0.02 M; Brij-P35 0.05 M; Triton-X-100 0.05 M and Tween 80 0.10 % (v/v). The
acetanilide (5 mg) was placed in a stoppered quartz cell provided with a stir bar (3 ml) and of the
surfactant stock solution (2 mL) was added. Then, the solution was vigorously stirred during one
hour and degassed with argon for additional 20 min. The quartz cell was placed in a homemade
optical bench provided with two germicide lamps (Philips, each of 20 Watts, purchased in
Argentina). The progress of the photoreaction was monitored by two different methods: (i) UV-
visible spectroscopy and GC analysis (Ultra 2 capillary column). The conversion of the amides was
kept below 20% to avoid secondary reactions and formation of by-products. Previous to injection
into the GC apparatus, the micellar solutions were treated as follow. The photolyzed solutions were
diluted with 2 mL of an aqueous solution of NaCl and then extracted with ethyl acetate (3x2 mL)
while the system was carefully shacked. The organic layer was separated, dried over Na2SO4 and
evaporated to dryness under vacuum. The yellowish solid residue was taken with dicloromethane

Photochemical & Photobiological Sciences
Page 6 of 22
(2.00 mL) and this new solution was injected into the GC for chromatographic analysis. The
View Article Online
DOI: 10.1039/C5PP00349K
products were characterized by comparison of physical constant (m.p.) and spectroscopical data
(1H-NMR and 13C-NMR) reported in the literature. These data and the corresponding references are
listed in Electronic Supplementary Information section. The substituted anilines 1c – 15c were
identified by comparison of their chromatographic characteristics with those of authentic
commercial samples.
Results and discussion.
Use of micelles of ionic and neutral surfactants to carry out photoreactions requires to knowledge of
1
the location of reactants in the system. We conducted UV-visible and H NMR studies of guest
molecules (acetanilides) within micelles to gain an understanding of the reactant’s positioning. Our
first approach was to determine the binding constant (Kb) between acetanilides and micelles using
UV-visible spectroscopy. Among of the guest acetanilides investigated, we have selected
acetanilides 4, 11, 12 and 13 which were soluble enough in water to record the UV-visible spectrum
and then, to determine the Kb. UV-visible spectra of 4 and 13 in water in the presence and absence
of surfactants Brij-P35 and CTAC, respectively, are presented in Fig. 1. Addition of increasing
amounts of surfactant produced both bathochromic and hyperchromic shifts of the lower energy
band. This spectroscopic behaviour demonstrates that 4 and 13 acetanilides bind to the micelle and
we propose that this molecular interaction takes place with the hydrophobic core of the micelle. A
similar behaviour was observed for acetanilides 11 and 12 and the UV-visible spectra are shown in
Fig. 1S (see ESI).
2.0
1.6
1.2
0.8
0.4
0.0
(a)
1.4
1.2
1.0
0.8
CTAC
CTAC
230
235
240
245
/ nm
250
255
260

200
250
300
350
400
 / nm

Page 7 of 22
Photochemical & Photobiological Sciences
View Article Online
DOI: 10.1039/C5PP00349K
2.0
1.6
1.2
0.8
0.4
0.0
(b)
1.4
1.2
1.0
0.8
Brij-P35
Brij-P35
230
240
250
260
270
280
 / nm
200
250
300
 / nm
350
400
Figure 1. UV-visible spectra of acetanilides. Effect of addition of surfactants in the acetanilide
water solution (room temperature): (a) acetanilide 13 with increasing concentration of CTAC and
(b) acetanilide 4 with increasing concentration of Brij-P35. Insets: partially spectrum magnification
showing the hyperchromic and bathochromic shifts for acetanilide 13 around 240 nm (Plot (a)) and
for acetanilide 4 around 247 nm (Plot (b)).
Furthermore, if the binding of the guest to the micelle can be described as an equilibrium, Kb
can be written according to Equation 1 where S are the acetanilides, Surf are the surfactants and [S-
Surf] are the complex acetanilides surfactants.
Kb
[S-Surf]
[Surf]
Kb
(1)
[S-Surf]
=
[Surf]
[S]
+
[S]
Application of Lambert-Beer law on Equation 1 gives Equation 2 where A and A0 are the
absorbance at the maxima wavelength in the presence and absence of surfactant, respectively, and
S and C are the molar absorptivity of the acetanilides and the complex. Rearranging Equation 2
provides Equation 3 where a linear relationship is observed between (A – A0)-1 and the reciprocal of
the concentration of the surfactant.
C.Kb.[Surf]
S.(1 + Kb.[Surf])
(A - A0)
A0
(2)
(3)
=
=
S
C
S
A0
1
A
1
A0
=
+
C.Kb
[Surf]
(A - A0)

Photochemical & Photobiological Sciences
Page 8 of 22
Fig. 2 shows the experimental data obtained for the systems acetanilides 4 - Brij-P35 and 13
View Article Online
DOI: 10.1039/C5PP00349K
- CTAC, respectively, and also show the best linear regression curves. The plots for the other
surfactants are shown in Fig. 2S (see ESI).
50
40
(a)
30
20
10
0
(b)
0
500
1000
1500
2000
2500
3000
1 / [Surfactant]
Figure 2. Plot of reciprocal of A vs reciprocal of concentration of surfactants in water at room
temperature: (a) acetanilide 13 with CTAC and (b) acetanilide 4 with Brij-P35.
From the ratio of the slope and the origin it was easily to calculate the Kb values which are collected
in Table 1 for acetanilides 4, 11, 12 and 13 with different surfactants. These data show that the
acetanilides bind to micelles and those who have a hydrophobic character, i.e. acetanilide 4, show
high values.
Table 1. Binding constant (Kb) in water of acetanilides 4, 11, 12 and 13 in the presence of different
surfactants at room temprature.
Kb / M-1
Acetanilides
SDS CTAC CTAB Brij-P35
109
7
552
11
459
32
214
63
4
11
12
13
17
81
135
76
113
70
58
33

Page 9 of 22
Photochemical & Photobiological Sciences
Savelli and co-workers have estimated a Kb value ≤ 100 M-1 for substrates that are not very
View Article Online
DOI: 10.1039/C5PP00349K
hydrophobic in SDS, CTAC and CTAB such as phenyl chloroformate.11 Furthermore, Quina,
Treiner and co-workers pointed out that these values of Kb are typical of organic solutes with aryl
moieties.12 This is the case for acetanilides 11, 12 and 13 whose Kb values are lower than 100 M-1.
This behaviour can be attributed to the fact that these acetanilides are enough soluble in water at the
concentration (≈ 1x10-5 M) that the UV-visible experiments were carried out. Noteworthy is the
case of acetanilide 11 where the Kb values in SDS, CATC and CTAB are very lower which is
attributed to the high solubility of the acetanilide in water. Acetanilide 4 is an example of a
hydrophobic amide. It is not much soluble in water at the concentration used in the UV-visible
experiments and the Kb values are near or greater than 100 M-1. Cabaleiro Lago and co-workers
have estimated the Kb values between a series of substituted benzoyl chlorides and the surfactant
and found that these values are higher than those obtained for CTAC and SDS.13 A minimum value
of Kb for surfactant Brij-P35 was estimated around 190 M-1 which account for a more apolar
environment using pyrene as a micropolarity probe. Therefore, the data collected in Table 1 for
acetanilides 4, 11 – 13 in this non-ionic surfactant show a similar trend that was observed for the
ionic surfactants.
With the aim to search the location of the acetanilides within the hydrophobic core of
1
micelles, we conducted H NMR studies of guest molecules within surfactant micelles to gain an
understanding of the reactant’s positioning. The NMR spectroscopy has been employed early to
assess the location of a solute within the micellar assembly.14 Among the fifteen guests investigated,
we selected acetanilides 1, 3, 5, 7, 8 and 11 and the surfactants CTAB, SDS and Brij-P35 for the 1D
and 2D 1H NMR spectroscopy study. 1H NMR of surfactants in D2O in the presence and absence of
acetanilides showed differential effects on the various protons of the surfactants, causing slightly
upfield and downfield shifts (˜ 0.1 – 0.01 ppm). The magnitudes of the change in the shifts are much
above the value for typical errors in the chemical shifts equal to 0.002 ppm.14c Table 2 shows the
differential chemical shifts for the CTAB in the presence of several acetanilides. Similar
spectroscopic behaviour was also observed for the surfactants SDS and Brij-P35 and the results are
shown in Table 2S (see ESI). The intimate interaction between the acetanilides and the hydrocarbon
chains of the surfactants has a significant role on the surfactants proton shift. Thus, the differential
chemical shifts shown in Tables 2 and 2S suggest that the acetanilides could be located in shell as
well as the hydrophobic core of surfactant micelles. This behaviour can be ascribed to the high
concentration of acetanilide solutes used in our NMR experiments that are preferentially solubilized
at the core/shell interface but spread further into the shell and the core of the micelle.14a

Photochemical & Photobiological Sciences
Page 10 of 22
Table 2. Differential chemical shift () of CTAB (70 mM) in the presence of acetanilides (10 mM)
View Article Online
DOI: 10.1039/C5PP00349K
in D2O at room temperature.
 / ppm


N
12

Br


N+(CH3)3
0.05
Acetanilides
-CH2
0.12
0.08
0.08
0.004
-CH2
0.11
0.06
0.08
-0.001
-CH2 -CH2 -CH3
-
-0.05
-0.01
-0.04
0.01
0.08
-0.03
-0.06
-0.02
1
3
5
8
0.04
0.03
-0.01
-
-
0.01
1
Additional H NMR studies have been carried out in order to confirm qualitatively the
location of the acetanilides within the micelle assembly. 2D NOESY experiments were performed
in D2O mixing a surfactant with an acetanilide in ca. 1:1 molar ratio. Fig. 3 shows a 2D NOESY
NMR spectrum for a solution of Brij-P35 (7 mM) in the presence of acetanilide 1 (10 mM) in D2O.
The inset green frames identify the Nuclear Overhauser Effect (NOE) between the signals of the
aromatic protons (H-2, H-3 and H-4) and the methyl protons (H-7) of acetanilide 1 and the signals
of the surfactant (H-1, H-2, H-5 and H-6). The numbering of the protons of the surfactant Brij-P35
and acetanilide 1 are shown in Fig. 3. Similar results were obtained for solutions of SDS and CTAB
in D2O in the presence of acetanilides 1, 7 and 11 and the corresponding 2D NOESY NMR spectra
are shown in Fig. 3S (see ESI). The intermolecular NOEs connecting the resonances of acetanilide
and surfactant are clearly visible in the figures confirming the results described with 1D NMR
spectroscopy. Although a precise positioning cannot be estimated with certainty, we can suggest
that the acetanilides are located in shell as well as the hydrophobic core of surfactant micelles
taking into account that the aromatic protons as well as the methyl protons of the acetanilides
correlates nicely with the different protons of the surfactants.
The NMR spectroscopic results encourage us to study the photochemical reaction of
substituted acetanilides in water – surfactant solutions as reaction media because working with
acetanilides concentration around or higher than 5.0x10-3 M warrant that the substrates are spread
within the shell/hydrophobic core of the micelle and the photoreaction is expected to take place
within the micelle.

Page 11 of 22
Photochemical & Photobiological Sciences
2
7
H5
H3
NH
3
4
O
HO
O
O
View Article Online
22
9
H6
H4
DOI: 10.1039/C5PP00349K
Acetanilide
H1
H2
Brij-P35
Figure 3. 2D NOESY spectrum of a solution of Brij-P35 (7 mM) and 1 (10 mM) in D2O at room
temperature.
To examine the capability of neutral and ionic micelles as a reaction medium to induce
photoproduct regio selectivity from aryl amides, the unimolecular photochemical reaction,
specifically the photo-Fries rearrangement of several substituted aryl acetamides and -naphthyl
acetamide (see Scheme 4) were investigated. In this reaction, upon irradiation, a molecule from its
singlet excited state fragment to form a radical pair. Depending upon the mobility and confinement
provided by the medium, the primary intermediates can yield various products as discussed below.
Irradiation of acetanilide (1) in cyclohexane, an isotropic medium that represents the
behavior of a guest in unrestricted environment, resulted in the formation of 45% 1a and 38% 1b
(Table 3). A small amount of cage escape product (1c) was also observed. Irradiation of acetanilide
1 in an aqueous solution in the presence of neutral and ionic surfactants yields 2-acetyl aniline (1a)
with noticeable selectivity and in high yield which is a quite different behavior compared to that in
cyclohexane (Table 3). The selectivity obtained within Brij-P35 surfactant is better (quantitative)
than that obtained within micelles from classical surfactant such as SDS, CTAC, CTAB, Tween 80,
and Triton-X100 where a significant amount of compound 1b (13-27%) was obtained. Further, no
aniline was observed when the irradiations of 1 were carried out in water in the presence of
surfactants which evidences the suppression of products arising from cage escape. In all the
experiments performed in water in the presence of surfactants, the concentration of surfactants was

Photochemical & Photobiological Sciences
Page 12 of 22
100 times higher than the cmc (see Table 3). Note that all photochemical reactions were kept at
View Article Online
15
DOI: 10.1039/C5PP00349K
about 20% conversion, which is a standard operating procedure in mechanistic photochemistry.
This avoids complications in analysis due to secondary photoreactions from the products of the
reaction under investigation.
Table 3. Irradiation of acetanilide (1) in cyclohexane and micellar media.
Yield (%)a
NH2
O
NH2
H2N
Solvent
Surfactante
O
1a
1b
38
17
1c
Cyclohexane
H2O
----
45
73
15
SDS (0.10 M)
H2O
Brij-P35 (0.05 M)
CTAC (0.02 M)
CTAB (0.02 M)
Tween 80b
> 99
66
H2O
27
22
23
13
H2O
68
H2O
72
H2O
Tritón X-100 (0.05 M)
85
a exc: 254 nm; Atmosphere: Ar; [Acetanilide]: 0.010 M; t: 360 min; T: 25ºC. b [Tween 80]: 0.10 %
v/v; t: 180 min.
Results presented above clearly demonstrate that the singlet radical pair A, i.e., anilinium
radical and acetyl radical (see Scheme 3), generated in the shell/core of the micellar assembly is
restrained within the cage eliminating diffusion into the aqueous phase, thereby no aniline (1c) was
obtained. Another important aspect, namely the higher ratio of products 1a:1b in the micellar
systems than in cyclohexane implies suppression of rotational freedom of the encapsulated
molecule in the micro heterogeneous medium. Therefore, we can conclude that the lack of cage
escape products and the selectivity of the photoreaction are due to a significant rigidity and
confinement of the micellar assembly. However, there exists some amount of rotation for radical
pair A within the long chain micelles, resulting in the formation of 1b.

Page 13 of 22
Photochemical & Photobiological Sciences
1
1
H
H
*
kdiff
View Article Online
DOI: 10.1039/C5PP00349K
NH
N
NH
N
h
O
O
O
O
bulk
NH2
micelle
1
A
NH2
O
NH2
+
+
O
1c
1a
1b
Scheme 3. Photochemical reaction of acetanilide in micellar media.
Next, we studied the photo-Fries rearrangement of several mono ortho- and para- and also
disubstituted acetanilides bearing electron donor and electron withdrawing groups in homogeneous
(cyclohexane) and micellar media. In Scheme 4 are shown the photoreactions of the acetanilides (2
– 15) together with the corresponding product distribution. The chemical yields of the
photoproducts are collected in Table 4.
The acetanilides 2 – 14 upon irradiation in cyclohexane afforded the migrated photoproducts
and the corresponding substituted anilines (Table 4). No selectivity was observed in homogeneous
media. Besides, when the photoreactions were performed in water – surfactants media noticeable
selectivity was observed. Irradiation of the para-substituted acetanilides bearing electron donor and
electron withdrawing substituents (2 – 5 and 7) afforded the ortho-migrated products (2a – 5a and
7a) in high to quantitative yields. However, in some few cases para-substituted anilines were
detected in very low yields (≤ 9%) showing again a significant inhibition of the out-of-cage escape
of the radical intermediates formed within the micelle.

Photochemical & Photobiological Sciences
Page 14 of 22
O
View Article Online
DOI: 10.1039/C5PP00349K
NH2
O
NH2
HN
h
+
Solvent
25 ºC
R
R
R
2; R = CH3
2a
3a
4a
5a
2c
3c
4c
5c
3; R = OCH3
4; R = OPh
5; R = Cl
6; R = CN
7; R = COCH3
8; R = NO2
6a
7a
8a
6c
7c
8c
O
NH2
NH2
O
NH2
R
NH
h
R
R
R
+
+
Solvent
25 ºC
O
9; R = CH3
10; R = Cl
9a
10a
9b
10b
9c
10c
O
NH2
O
O
NH2
NH2
NH
h
+
+
Solvent
25 ºC
OCH3
OCH3
14b
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
14
14a
14c
NH2
O
NH2
NH2
O
HN
h
+
+
Solvent
25 ºC
O
15
15a
15b
15c
Scheme 4. Photoreaction of acetanilides 2 – 15.
Irradiation of compound 6 in all the micellar media gives the desired ortho-migrated
photoproduct (6a) in good yields together with significant amounts (22 – 37%) of p-cyanoaniline
6c. When surfactant Brij-P35 was used the photochemical reaction gives 6a in quantitative yield
(Table 4). We attributed the formation of 6c due to the partial solubility of acetanilide 6 in water
where the photoreaction takes place simultaneously within the micellar assembly and in the bulk.
When 4-nitro acetanilide (8) was irradiated in isotropic and anisotropic media for 12 h no
photo-Fries rearrangement took place recovering quantitatively the starting material. This behavior
can be explained because nitroarenes show a high intersystem-crossing quantum yield (ISC = ca.

Page 15 of 22
Photochemical & Photobiological Sciences
0.50) and hence, a change in the multiplicity of the excited state from singlet to triplet excited state
View Article Online
DOI: 10.1039/C5PP00349K
16
is promoted. Therefore, we proposed that population of the triplet excited state of acetanilide 8 is
favored because the photo-Fries reaction of acetanilides takes place from the singlet excited state,3
and no reaction occurs from the triplet excited state of acetanilide 8.
Table 4. Irradiation of acetanilides (2 – 7 and 9 – 15) in cyclohexane and water – surfactant media.
Acetanilides
Mediumb
2
3
4
5
6
7
Yield (%)a
2a
48
88
2c
28
9
3a
49
95
> 99
> 99
> 99
> 99
3c
26
2
4a
62
93
> 99
> 99
> 99
90
4c
28
6
5a
42
98
5c
25
6a
64
88
> 99
73
80
6c
35
7a
48
7c
41
Cyclohexane
SDS
22 > 99
---
27 > 99
20 > 99
37 > 99
15
Brij
CTAC
CTAB
95
2
97
> 99
> 99
90
> 99
> 99
> 99
Triton X-100
Acetanilides
Mediumb
7
9
5
63
10
14
Yield (%)a,c
9a
42
67
73
64
70
70
9b
30
33
27
36
30
30
9c
15
10a 10b 10c 14a 14b 14c 15a 15b 15c
Cyclohexane
SDS
39
66
69
54
61
27
34
31
46
36
16
51
63
73
70
51
63
17
25
17
14
17
25
15
40
94
97
98
95
93
35
15
5
Brij
CTAC
CTAB
15
1
2
Triton X-100
>99
aexc: 254 nm; Atmosphere: Ar; [Acetanilides]: 0.010 M; T: 25 ºC. Concentration of the
b
c
surfactants in water as indicated in Table 3; Irradiation of compound 15 (0.010 M) with exc: 310
nm.
Irradiation of ortho-substituted acetanilides 9 and 10 in micellar solution showed a
noticeable selectivity (see Table 4). No substituted anilines (9c and 10c) were formed while the
migrated photoproducts were obtained in fairly good yield. The migration of the acetyl group to the
ortho position of the phenyl moiety is favored over the para position giving an ortho:para ratio ca.
2:1. Noteworthy, irradiation of compound 10 in water – Triton X-100 media gives product 10a in
quantitative yield. A similar behavior was observed for the irradiation of 3,4-dimethoxy acetanilide
(14) in micellar media. Photoproducts 14a and 14b were formed exclusively, where 14a was always
formed in yields higher than 14b; aniline 14c was not detected in the reaction mixture (see Table 4).
This selectivity arises from the fact that because of steric hindrance acetyl radical migrates
preferentially to C – 6 than to C – 2 of the aromatic moiety.
Finally, a polycyclic aryl amide such as -naphthyl acetamide (15) was also irradiated in
cyclohexane at exc 310 nm rendering the expected photoproducts 15a, 15b and 15c (see Table 4).
When the photo-Fries reaction of 15 was carried out in micellar solutions compound 15a was

Photochemical & Photobiological Sciences
Page 16 of 22
formed in excellent yields independent of the nature of the surfactant employed. In few cases,
View Article Online
DOI: 10.1039/C5PP00349K
photoproducts 15b and 15c were detected in the reaction mixture in very low yields.
Noteworthy, the irradiation of acetanilides 1, 9 and 10 do not provide the ortho rearranged
photoproducts with high selectivity as was observed for the case of the p-substituted acetanilides (2
– 5 and 7). This behaviour can be attributed to the less rigidity and confinement of conventional
small molecules surfactant micelles when are compared to more rigid and confined environment
such as amphiphilic homopolymers nanopocket, capsule formed by a deep cavity cavitand and bile
salt micelles.1l,1m,1n Therefore, the loss of rigidity of the micelles favoured the mobility of the singlet
radical pairs inside the micelle rendering the corresponding para rearranged photoproducts (1b, 9b
and 10b) in significant amounts (see Table 4). Thus, the flexibility of the micelles allow to the
acetyl radical to reach the para position of the anilinium radical formed during the irradiation.
Similar conclusions have been reached by Ramamurthy and co-workers when studied the photo-
Fries rearrangement of naphthyl esters in amphiphilic homopolymers and conventional surfactant
micelles water solutions.
The photochemical reaction of acetanilides 1 – 7 and 9 – 15 within micellar assembly
showed a noticeable selectivity favouring the formation of the ortho regioisomers over the escape
photoproducts, viz. anilines. However, significant amounts of the para regioisomers are obtained for
acetanilides 1, 9 and 10. The photoreaction proceeded efficiently with a variety of electron donor
and electron withdrawing substituents at para and ortho position of the aryl moiety. Also, -
naphthyl acetamide, a polycyclic aryl moiety, rearranged with selectivity and high efficiency. These
results showed the applicability of the sustainable water surfactant media in the preparation of
ortho-amino phenones as an alternative and efficient methodology in organic synthesis.
Conclusions.
The photo-Fries reaction of the included photoactive acetanilides has helped establish
surfactant micelle assemblies as capable of affecting selectivity of this reaction by restricting the
freedom of the reactive intermediates. Inclusion of the substrates in the shell as well as in the
1
hydrophobic core of the micelles have been established and confirmed by 1D and 2D H-NMR
spectroscopies. A noticeable selectivity in product distribution was observed in anisotropic media
affording the ortho-migrated photoproducts with good to excellent yields. In all cases it is clear that
inhibition of out-of-cage products, viz. anilines, occurs efficiently which means that the micelle
assembly is enough rigid to prevent radical escape and/or to behave as a free radical scavenger.
Another interesting feature of micelle assembly is the effectiveness in dictating the behavior of
singlet radical pairs suggesting that the micelles are able to constrict the mobility of short-lived

Page 17 of 22
Photochemical & Photobiological Sciences
radical pairs to some extent. However, significant amounts of the para regioisomers are obtained
View Article Online
DOI: 10.1039/C5PP00349K
from acetanilides 1, 9 and 10. From a synthetic viewpoint, micellar media is a sustainable and
alternative media that provides 2-acetyl anilines in excellent yields which are useful synthons in the
preparation of quinolones.
Acknowledgement.
The authors thank Universidad de Buenos Aires (X 0055BA), CONICET (PIP0072CO and
PIP0155) and ANPCyT (PICT 2012-0888) for financial support. R.E.B. and S.M.B. are research
members of CONICET. D. Iguchi was recipendant of a scholarship from CONICET (Doctorate
Program).
Note and References.
1 a) M. A. Miranda, F. Galindo in Photochemistry of Organic Molecules in isotropic and
Anisotropic Media, eds. V. Ramamurthy, K. S. Schanze, Marcel Dekker, New York, 2003, Chapter
2; b) A. Natarajan, L. S. Kaanumale, V. Ramamurthy in CRC Handbook of Organic Photochemistry
and Photobiology, eds. W. Horspool, F. Lenci, CRC Press, Boca Raton, FL, 2004, Vol. 3, p. 107; c)
J. H. Fendler, E. J. Fendler in Catalysis in Micellar and Macromolecular System, Academic Press,
London, 1975; d) Mixed Surfactant System, eds. P. M. Holland, D. N. Rubingh, American Chemical
Society, Washington, DC, 1994; e) N. J. Turro, From Boiling Stones to Smart Crystals:ꢀ
Supramolecular and Magnetic Isotope Control of Radical−Radical Reactions in Zeolites, Acc.
Chem. Res., 2000, 33, 637-646; f) K. Bhattachrya, Solvation Dynamics and Proton Transfer in
Supramolecular Assemblies, Acc. Chem. Res., 2003, 36, 95-101; g) C. H. Tung, L. Z. Wu, L. P.
Zhang, B. Cheng, Supramolecular Systems as Microreactors:ꢀ Control of Product Selectivity in
Organic Phototransformation, Acc. Chem. Res. 2003, 36, 39-47; h) R. S. H. Liu, G. S. Hammond,
Reflection on Medium Effects on Photochemical Reactivity, Acc. Chem. Res., 2005, 38, 396-403; i)
W. Gu, R. G. Weiss, Extracting fundamental photochemical and photophysical information from
photorearrangements of aryl phenylacylates and aryl benzyl ethers in media comprised of
polyolefinic films, J. Photochem. Photobiol. C: Photochemistry Reviews, 2001, 2, 117-137; j) V.
Ramamurthy, Controlling photochemical reactions via confinement: zeolites, J. Photochem.
Photobiol. C: Photochemistry Reviews, 2000, 1, 145-166; k) L. S. Kaanumalle, J. Nithyanandhan,
M. Pattabiaman, N. Jayaraman, V. Ramamurthy, Water-Soluble Dendrimers as Photochemical
Reaction Media:ꢀ Chemical Behavior of Singlet and Triplet Radical Pairs Inside Dendritic Reaction
Cavities, J. Am. Chem. Soc., 2004, 126, 8999-9006; l) S. Arumugan, D. R. Vutukuri, S.
Thayumanavan, V. Ramamurthy, Amphiphilic Homopolymer as a Reaction Medium in Water:ꢀ

Photochemical & Photobiological Sciences
Page 18 of 22
Product Selectivity within Polymeric Nanopockets, J. Am. Chem. Soc., 2005, 127, 13200-13206; m)
View Article Online
DOI: 10.1039/C5PP00349K
M. Pattabiraman, L. S. Kaanumalle, V. Ramamurthy, Photoproduct Selectivity in Reactions
Involving Singlet and Triplet Excited States within Bile Salt Micelles, Langmuir, 2006, 22, 2185-
2192; n) L. S. Kaanumalle, C. L. D. Gibb, B. C. Gibb, V. Ramamurthy, Photo-Fries
reaction in water made selective with a capsule, Org. Biomol. Chem., 2007, 5, 236-238; o) R.
Kulasekharan, R. Choudhurry, R. Prabhakar, V. Ramamurthy, Restricted rotation due to the lack of
free space within a capsule translates into product selectivity: photochemistry of cyclohexyl phenyl
ketones within a water-soluble organic capsule, Chem. Commun., 2011, 47, 2841-2843.
2 J. C. Anderson, C. B. Reese, Photoinduced Fries rearrangement, Proc. Chem. Soc. London, 1960,
217.
3 a) D. Bellus, Photo-Fries rearrangement and related photochemical [1,j] – shift (j: 3, 5, 7) of
carbonyl and sulfonyl groups, Adv. Photochem., 1971, 8, 109-159; b) M. A. Miranda in CRC
Handbook of Organic Photochemistry and Photobiology, eds. W. Horspool, P. S. Song, CRC Press,
Boca Raton, FL, 1995, p. 570.
4 a) J. W. Meyer, G. S. Hammond, Mechanism of photochemical reactions in solution. LXX.
Photolysis of aryl esters, J. Am. Chem. Soc., 1972, 94, 2219-2228; b) C. E. Kalmus, D. S. Hercules,
Thermal .pi.-route rearrangement of 4-cycloheptene-1-methyl acetate, J. Am. Chem. Soc., 1974, 96,
449-460; c) N. P. Gristan, Y. P. Tsentalovich, A. V. Yurkovskay, R. Z. Sagdeev, Laser Flash
Photolysis and CIDNP Studies of 1-Naphthyl Acetate Photo-Fries Rearrangement, J. Phys. Chem., 1996,
100, 4448-4458; d) S. M. Bonesi, L. K. Crevatin, R. Erra Balsells, Photochemistry of 2-
acyloxycarbazoles. A potential tool in the synthesis of carbazole alkaloids, Photochem. Photobiol.
Sci,. 2004, 3, 381; e) L. C. Crevatin, S. M. Bonesi, R. Erra Balsells, Photo-Fries rearrangement of
Carbazol-2-yl Sulfonates. Efficient tool for the introduction of sulfonyl groups into polycyclic
aromatic compounds, Helv. Chim. Acta, 2006, 89, 1147.
5 a) H. Shizuka, I. Tanaka, Photochemistry of Acetanilide. I. Quantum Yields of the Rearrangement
and Benzene Photosensitized Reaction, Bull. Chem. Soc. Jpn., 1968, 41, 2343-2349; b) H. Shizuka,
Photochemistry of Acetanilide. II. The Primary Processes in the Photochemical Reaction, Bull.
Chem. Soc. Jpn., 1969, 42, 52-57; c) H. Shizuka, Photochemistry of Acetanilide. III. The Secondary
Processes in the Photochemical Reaction, Bull. Chem. Soc. Jpn., 1969, 42, 57-65; d) H. Shizuka, M.
Kato, T. Ochaiai, K. Matsui, T. Morita, The Photochemical Rearrangement of Phenyl Acetate, Bull.
Chem. Soc. Jpn., 1969, 42, 1831-1836; e) H. Shizuka, M. Kato, T. Ochaiai, K. Matsui, I. Tanaka,
The Photochemical Rearrangements of N-Acetyl Diphenylamine and N-Acetyl Carbazole, Bull.
Chem. Soc. Jpn., 1970, 43, 67-74; f) S. M. Bonesi, R. Erra Balsells, Product Study of the photolysis
of N-acetyl carbazole in ethanol and dichloromethane solution. Part I, J. Photochem. Photobiol. A:
Chem., 1991, 56, 55; g) S. M. Bonesi, R. Erra Balsells, Photochemical behaviour of N-acetyl and

Page 19 of 22
Photochemical & Photobiological Sciences
N-benzoyl carbazole: photo-Fries rearrangenent and photoinduced single electron transfer, J.
View Article Online
DOI: 10.1039/C5PP00349K
Photochem. Photobiol. A: Chem., 1997, 110, 271.
6 F. M. Menger, The structure of micelles, Acc. Chem. Res., 1979, 12, 111-117.
7 a) N. J. Turro, J. Mattay, Photochemistry of some deoxybenzoins in micellar solutions. Cage
effects, isotope effects, and magnetic field effects, J. Am. Chem. Soc., 1981, 103, 4200-4204; b) N.
J. Turro, G. Sidney Cox, M. A. Paczkowski, Photochemistry in Micelles in Topics in Current
Chemistry, Photochemistry and Organic Synthesis, ed. F.L. Boschke, Springer-Verlag, New York,
1985, 129, 57.
8 a) N. J. Turro and B. Kraeutler, Magnetic field and magnetic isotope effects in organic
photochemical reactions. A novel probe of reaction mechanisms and a method for enrichment of
magnetic isotopes, Acc. Chem. Res., 1980, 13, 369-377; b) N. J. Turro, A. L. Buchachenko, V. F.
Tarasov, How Spin Stereochemistry Severely Complicates the Formation of a Carbon-Carbon Bond
between Two Reactive Radicals in a Supercage, Acc. Chem. Res., 1995, 28, 69-80; c) K.
Lalyanasundaran in Photochemistry in Microheterogeneous Systems, Academic Press, Inc.,
Orlando, FL, 1987.
9 a) A. K. Singh, T. S. Raghuraman, Photorearrangement of phenyl cinnamates under micellar
environment, Tet. Lett., 1985, 26, 4125-4128; b) R. Nakagaki, M. Hiramatsu, T. Watanabe, Y.
Tanimoto, S. Nagakura, Magnetic isotope and external magnetic field effects upon the photo-Fries
rearrangement of 1-naphthyl acetate, J. Phys. Chem., 1985, 89, 3222-3226; c) R. Q. Yie, Y. C. Liu,
X. G. Lei, The photo-fries rearrangement of α-naphthyl acetate in cyclodextrin and micelle,
Res. Chem. Intermed., 1992, 18, 61-69; d) B. Suau, G. Torres, M. Valpuesta, The photo-fries
rearrangement of 2,5-disubstituted phenyl acetates, Tet. Lett., 1995, 36, 1311-1314; e) M.
Nowakowska, J. Storsberg, S. Zapotoczny, J. E. Guillet, Studies of the antenna effect in polymer
molecules. 28. Photo-Fries rearrangement of 1-naphthyl acetate in aqueous solutions of
poly(sodium styrenesulfonate-co-2-vinylfluorene), New J. Chem., 1999, 23, 617-623; f) A. K.
Singh, T. S. Raghuraman, Photobehaviour of N-Aryl Amides in Micelle, Synth. Commun., 1986, 16,
485-490; g) M. S. Syamala, B. Nageswer Rao, V. Ramamurthy, Modification of Photochemical
Reactivity by Cyclodextrin complexation: Product Selectivity in Photo-Fries Rearrangement,
Tetrahedron, 1988, 44, 7234-7242; h) M. Nasetta, R. H. De Rossi, J. J. Cosa, Influence of
Cyclodextrins on the Photo-Fries rearrangement of acetanilide, Can. J. Chem., 1988, 66, 2794-
2798.
10 a) Ch. Felnon, H. Cynamon, Synthesis and Antibacterial Activities of Optically Active
Ofloxacin, Antimicrob. Agents Chemother., 1986, 29, 163-164; b) K. Drlica, X. Zhao, DNA gyrase,
topoisomerase IV, and the 4-quinolones, Microbiol. Mol. Biol. Rev., 1997, 61, 377-392; c) A. F.
Pazkarshii, A. Soldatinkov., A. R. Katritzky in Heterocyles in life and society, John Wiley and

Photochemical & Photobiological Sciences
Page 20 of 22
Sons, Chichester, 1997, p. 147 – 148; d) D. Edmont, R. Rocher, C. Plisson, J. Chenault, Synthesis
View Article Online
DOI: 10.1039/C5PP00349K
and evaluation of quinoline carboxyguanidines as antidiabetic agents, Bioorg. Med. Chem. Lett.,
2000, 10, 1831-1834; e) Y. Xia, Z-Y. Yang, P. Xia, K. F. Bastow, Y. Nakanishi, P. Nampoothiri, E.
Hamel, A. Brossi, K-H. Lee, Antitumor Agents. Part 226:y Synthesis and Cytotoxicity of 2-Phenyl-
4-quinolone Acetic Acids and Their Esters, Bioorg. Med. Chem. Lett., 2003, 13, 2891-2893; f) L. A.
Mitscher, Bacterial Topoisomerase Inhibitors:ꢀ Quinolone and Pyridone Antibacterial Agents,
Chem. Rev., 2005, 105, 559-592; g) S. Nakamura, M. Kozuka, K. F. Bastow, H. Tokuda, H.
Nishino, M. Suzuki, J. Tatsuzaki, S. L. M. Natschke, S-C. Kuo, K-H. Lee, Cancer preventive
agents, Part 2: Synthesis and evaluation of 2-phenyl-4-quinolone and 9-oxo-9,10-dihydroacridine
derivatives as novel antitumor promoters, Bioorg. Med. Chem., 2005, 13, 4396-4401; h) B. d’A.
Lucero, C. R. B.Gomes, I. C. Frugulhetti, L. V. Faro, L. Alvarenza, M. C. B. V. Souza, T. M. L. de
Souza, V. F. Ferreira, Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues, Bioorg.
Med. Chem. Lett., 2006, 16, 1010-1013; i) C. P. Jones, K. W. Anderson, S. L. Buchwald, Sequential
Cu-Catalyzed Amidation-Base-Mediated Camps Cyclization: A Two-Step Synthesis of 2-Aryl-4-
quinolones from o-Halophenones, J. Org. Chem., 2007, 72, 7968-7973; j) J. Huang, Y. Chen, A. O.
King, M. Dilmeghani, R. D. Larsen, M. M. Faul, A Mild, One-Pot Synthesis of 4-Quinolones via
Sequential Pd-Catalyzed Amidation and Base-Promoted Cyclization, Org. Lett., 2008, 10, 2609-
2611; k) T. Zhao, B. Xu, Palladium-Catalyzed Tandem Amination Reaction for the Synthesis of 4-
Quinolones, Org. Lett., 2010, 12, 121-215.
11 L. Brinchi, P. di Profio, F. Micheli, R. Germani, G. Savelli, C. A. Bunton, Structure of Micellar
head-Groups and the Hydrolysis of Phenyl Chlorofomate. The Role of Perchlorate Ion, Eur. J. Org.
Chem., 2001, 1115.
12 (a) L. Sepulveda, E. Lissi, F. H. Quina, Interactions of Neutral Molecules with Ionic Micelles, Adv.
Colloid Interface Sci., 1986, 25, 1-57; (b) F. H. Quina, E. O. Alonso, Incorporation of Nonionic
Solutes into Aqueous Micelles: A Linear Solvation Free Energy Relationship Analysis, J. Phys. Chem.,
1995, 99, 11708-11714; (c) H. Abraham, H. S. Chadha, J. P. Dixon, C. Rafols, C. Treiner,
Hydrogen bonding Part 40. Factors that influence the distribution of solutes between water and
sodium dodecylsulfate micelles, J. Chem. Soc., Perkin Trans. 2, 1995, 887-894; (d) H. Abraham,
H. S. Chadha, J. P. Dixon, C. Rafols, C. Treiner, Hydrogen bonding. Part 41.1 Factors that
influence the distribution of solutes between water and hexadecylpyridinium chloride micellesJ.
Chem. Soc., Perkin Trans. 2, 1997, 19-24.
13 P. Campos rey, C. cabaleiro lago, P. Hervés, Solvolysis of Substituted benzoyl Chlorides in
Nonionic and Mixed Micllar Solutions, J. Phys. Chem. B, 2010, 114, 14004 – 14011.
14 a) D. J. Luning Prak, W. I. Jahraus, J. M. Sims, A. H. Roy McArthur, An 1H NMR investigation
into the loci of solubilization of 4-nitrotoluene, 2,6-dinitrotoluene, and 2,4,6-trinitrotoluene in

Page 21 of 22
Photochemical & Photobiological Sciences
nonionic surfactant micelles, Colloids and Surfaces A: Physicochem. Eng. Aspects, 2011, 375, 12–
View Article Online
DOI: 10.1039/C5PP00349K
22; b) P. Sabatino, A. Szczygielb, D. Sinnaeveb, M. Hakimhashemia, H. Saveyna, J. C. Martinsb,
P. Van der Meerena, NMR study of the influence of pH on phenol sorption in cationic CTAB
micellar solutions, Colloids and Surfaces A: Physicochem. Eng. Aspects, 2010, 370, 42-48; c) L. A.
Bernardez, Investigation on the locus of solubilization of polycyclic aromatic hydrocarbons in non-
ionic surfactant micelles with 1H NMR spectroscopy, Colloids and Surfaces A: Physicochem. Eng.
Aspects, 2008, 324, 71-78; d) M. E. N. P. Ribeiro, C. L. de Moura, M. G. S. Vieira, N. V. Gramosa,
Ch. Chaubundit, M. C. de Mattos, D. Attwood, S. G. Yeats, S. K. Nixon, N. M. P. A. Ricardo,
Solubilisation capacity of Brij surfactants, International Journal of Pharmaceutics, 2012, 436, 631-
635; e) N. Dharaiyaa, S. Chavdaa, K. Singhb, D. G. Marangonib, P. Bahadura, Spectral and
hydrodynamic studies on p-toluidine induced growth in cationic micelle, Spectrochimica Acta Part
A, 2012, 93, 306-312; f) J. C. Eriksson, NMR-Experiments on Solubilization in Soap Micelles, Acta
Chem. Scand., 1963, 17, 1478-1481; g) J. C. Eriksson, G. Gillberg, NMR-Studies of the
Solubilisation of Aromatic Compounds in Cetyltrimethylammonium Bromide Solution. II., Acta
Chem. Scand., 1966, 20, 2019-2027; h) J.E. Gordon, J.C. Robertson, R.L. Thorne, Medium effects
on hydrogen-1 chemical shift of benzene in micellar and nonmicellar aqueous solutions of organic
salts, J. Phys. Chem., 1970, 74, 957-961; i) F. Podo, A. Ray, G. Nemethy, Structure and hydration
of nonionic detergent micelles. High resolution nuclear magnetic resonance study, J. Am. Chem.
Soc., 1973, 95, 6164-6171; j) X. Gao, T.C. Wong, Studies of the binding and structure of
adrenocorticotropin peptides in membrane mimics by NMR spectroscopy and pulsed-field gradient
diffusion, Biophys. J., 1998, 74, 1871-1888; k) X. Gao, T.C. Wong, NMR studies of
adrenocorticotropin hormone peptides in sodium dodecylsulfate and dodecylphosphocholine
micelles: Proline isomerism and interactions of the peptides with micelles, Biopolymers, 2001, 58
20-32; l) C. Chatterjee, C. Mukhopadhyay, Conformational alteration of bradykinin in presence of
GM1 micelle, Biochem. Biophys. Res. Commun., 2004, 315, 866-871; m) C. Chatterjee, C.
Mukhopadhyay, Interaction and structural study of kinin peptide bradykinin and ganglioside
monosialylated 1 micelle, Biopolymers, 2005, 78, 197-205; n) N. Matsumori, T. Houdai, M.
Murata, Conformation and Position of Membrane-Bound Amphotericin B Deduced from NMR in
SDS Micelles, J. Org. Chem., 2007, 72, 700-707; o) L. A. Bernardez, S. Ghoshal, Selective
Solubilization of Polycyclic Aromatic Hydrocarbons from Multicomponent Nonaqueous-Phase
Liquids into Nonionic Surfactant Micelles, Environ. Sci. Technol., 2004, 38, 5878-5887; p) M. S.
Goldenberg, L. A. Bruno, E. L. Rennwantz, Determination of Solubilization Sites and Efficiency of
Water-Insoluble Agents in Ethylene Oxide-Containing Nonionic Micelles, J. Colloid Interface Sci.,
1993, 158, 351-363.

Photochemical & Photobiological Sciences
Page 22 of 22
15 For examples, see: a) T. Mori, Y. Inoue, R. G. Weiss, Enhanced Photodecarboxylation of an
View Article Online
DOI: 10.1039/C5PP00349K
Aryl Ester in Polyethylene Films, Org. Lett., 2003, 5, 4661-4664; b) T. Hirano, W. Li, L. Abrams,
P. J. Krusic, M. F. Ottaviani, N. J. Turro, Supramolecular Steric Effects as the Means of Making
Reactive Carbon Radicals Persistent. Quantitative Characterization of the External Surface of MFI
Zeolites through a Persistent Radical Probe and a Langmuir Adsorption Isotherm, J. Org. Chem.,
2000, 65, 1319-1330; c) C. Cui, R. G. Weiss, Photo-Fries rearrangements of 2-naphthyl acylates as
probes of the size and shape of guest sites afforded by unstretched and stretched low-density
polyethylene films. A case of remarkable selectivity, J. Am. Chem. Soc., 1993, 115, 9820-9821.
16 a) S. M. Bonesi, M. Mesaros, F. M. Cabrerizo, M. A. Ponce, G. Bilmes, R. Erra-Balsells, The
photophysiscs of nitrocarbazoles used as UV-MALDI matrices. Comparative spectroscopic and
optoacoustic studies of mono- and dinitrocarbazoles Chem. Phys. Lett., 2007, 446, 49; b) A. Cors,
S. M. Bonesi, S. M.; R. Erra-Balsells, R., Photoreduction of nitroarenes with formic acid in
acetonitrile at room temperature, Tetrahedron Lett., 2008, 49, 1555.
Graphical abstract.
NMR spectroscopy show the location of acetanilides within the shell and the hydrophobic core of
micellar solutions. Irradiation of acetanilides in aqueous micellar solutions involves C-N homolytic
cleavage to yield singlet radical pairs that provide selectively 2-aminoacetophenone derivatives in
good to excellent yields.
Photo-Fries
H
rearrangement
Micellar media
High Selectivity
NH2
NH2
NH2
O
N
+
R
h
h
R
R
R
O
O
R
Organic
Solvents
25 °C
Surfactant
water
25 °C
R = H; CH3; Cl; OPh;
OCH3; CN; etc.
+
NH2
O