Modulation of reactivity of singlet radical pair in continuous flow: Photo-Fries rearrangement

Article abstract of DOI:10.1016/j.jphotochem.2018.06.014

Photo-Fries rearrangement of phenyl benzoate is studied using continuous flow for modulating the reactivity of singlet radical pair by changing the viscosity of the solvent. The effect of flow and proximity of the reactants with the light source on the reactivity of radical pair, formed from singlet excited state was investigated in details. In non-viscous solvent, the results from flow synthesis were comparable to batch reactor. In viscous solvents, selectivity of ortho- and para-isomers (o-/p- isomer) of the product could be controlled by changing viscosity as well as the flow rate. Using flow synthesis, ortho- and para-isomer ratio was obtained as high as 8.45 which are twice as compared to batch experiment with in fraction of residence time.

Full text of DOI:10.1016/j.jphotochem.2018.06.014

JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
Contents lists available at ScienceDirect
Journal of Photochemistry & Photobiology A: Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Modulation of reactivity of singlet radical pair in continuous flow: Photo-
Fries rearrangement
Neeta Karjulea,c, Mrityunjay K. Sharmab,c, Jayaraj Nithyanandhana,c, , Amol A. Kulkarnib,c,
⁎
⁎⁎
a
Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune, 411 008, India
Chemical Engineering & Process Development Division, CSIR-National Chemical Laboratory, Pune, 411 008, India
Academy of Scientific and Innovative Research, New Delhi, 110025, India
b
c
A R T I C L E I N F O
A B S T R A C T
Keywords:
Photo-Fries rearrangement of phenyl benzoate is studied using continuous flow for modulating the reactivity of
singlet radical pair by changing the viscosity of the solvent. The effect of flow and proximity of the reactants with
the light source on the reactivity of radical pair, formed from singlet excited state was investigated in details. In
non-viscous solvent, the results from flow synthesis were comparable to batch reactor. In viscous solvents, se-
lectivity of ortho- and para-isomers (o-/p- isomer) of the product could be controlled by changing viscosity as
well as the flow rate. Using flow synthesis, ortho- and para-isomer ratio was obtained as high as 8.45 which are
twice as compared to batch experiment with in fraction of residence time.
Photo-fries rearrangement
Flow photo chemistry
o-/p-Isomer
Batch
Continuous
Residence time
1. Introduction
irradiation, narrow residence time distribution and an ability to extend
the laboratory scale synthesis to large scale production [9–11]. The
The photochemical reaction for the selective synthesis of a desired
product involves an intermediate having short life time that mostly
requires activation free reaction pathways and hence it is a challenging
task. There are various approaches that have been adopted to increase
the selectivity by using wavelength specific chemical transformations
while the extent of reactions can be enhanced significantly by using
small confined domains for reaction to ensure that ample photo-gen-
erated species are available for the synthesis [1,2]. Molecules enclosed
in confined spaces in viscous solvents are expected to experience re-
strictions on their motion when compared to the open systems. A re-
striction of translational or rotational freedom of molecules as well as
the intermediates often gets reflected in the product distribution [3–5].
In the photo-fries rearrangement of phenyl esters the reaction proceeds
though an initial cleavage of phenyl ester to produce a phenoxy and an
acyl radical in a solvent cage which may recombine in different ways
and gives ortho- and para-isomers of hydroxybenzophenones [6,7]. The
formation of ortho- isomer requires less translational motion of one of
the radicals than what is needed for the formation of para-isomer. In
most of the cases formation of ortho- and para-isomer may dictate the
mobility of the radical species involved in the reaction, and this hy-
pothesis has been proved by utilization of highly viscous liquid in which
only ortho-isomer has been observed [8]. Flow photo chemistry in
small, optically transparent channels offers excellent mixing, uniform
Small flow dimensions offer large optically active area per unit volume
of the substrates, which helps to enhance the reaction rates significantly
[12]. The pumping action that generates convective flows with specific
flow profiles helps to have relatively narrow residence time distribution
compared to conventional mixed flow reactors [13]. In most of the
literature, the continuous photochemical reactor is usually a helical coil
or a micro-fabricated silica chip [14–16] having one side bound to
glass/quartz to facilitate the irradiation. In the helical coils, radius of
curvature decides the extent of secondary flow which reduces the axial
dispersion in the flow path. A review by Oelgemöller [9,11], Knowels
[17], Su and co-workers [18] gives a detailed account of several suc-
cessful examples of flow photochemistry. Among many, few of the ex-
cellent examples include [19–25]: (i) photocyanation of pyrene across
an oil/water interface in a polymer microchannel chip, (ii) continuous
flow photolysis of aryl azides, (iii) continuous flow synthesis of acti-
vated vitamin D3 and its analogues, (iv) flow assisted intramolecular
photocycloaddition of 1-cyanonaphthalene derivative, v) photo re-
arrangement reactions [26] (vi) singlet oxygen involved photochemical
reactions [27] and (vii) continuous flow photopolymerization.
Here we have studied continuous flow Photo-Fries rearrangement of
phenyl benzoate for getting complete conversion in short residence
time (Fig. 1) The advantage of flow chemistry to achieve improved
conversion due to superior light penetration, and control over residence
⁎
Corresponding author at: Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune, 411 008, India.
Corresponding author at: Chemical Engineering & Process Development Division, CSIR-National Chemical Laboratory, Pune, 411 008, India.
⁎⁎
E-mail addresses: j.nithyanandhan@ncl.res.in (J. Nithyanandhan), aa.kulkarni@ncl.res.in (A.A. Kulkarni).
https://doi.org/10.1016/j.jphotochem.2018.06.014
Received 16 February 2018; Received in revised form 7 May 2018; Accepted 5 June 2018
Availableonline06June2018
1010-6030/©2018ElsevierB.V.Allrightsreserved.

N. Karjule et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
plotted vs. concentration to get calibration trends for each compound.
Since all the data followed linear trends (given in SI) the slope of these
lines was further used for calculating the percentage conversion and
product distribution.
2.3. Synthesis of phenyl benzoate (1)
In a round bottom flask, first we dissolved benzoyl chloride
(0.83 mL, 7.1 mmol) in 15 mL of dichloromethane and then stirred it
well at 0 °C. To this solution, triethyl amine (1.98 mL, 14.2 mmol) was
added dropwise followed by mixture of phenol (0.69 mL, 7.81 mmol)
and dichloromethane (5 mL), and stirred it overnight at room tem-
perature. After overnight stirring this mixture was poured into ice cold
water followed by its extraction with dichloromethane. The organic
layer was washed with water and dried over Na2SO4. Then solvent was
evaporated and then the reaction mixture was purified by column
chromatography to afford phenyl benzoate (1.23 g, 88%) as a white
solid powder. 1H NMR (200 MHz, CDCl3) δ: 7.11–7.25 (m, 3 H),
7.31–7.39 (m, 2 H), 7.39–7.50 (m, 2 H), 7.52–7.62 (m, 1 H), 8.10–8.19
(m, 2 H).
2.4. General procedure for photo-fries rearrangement reaction in batch
reactor
Desired concentration of phenyl benzoate solution was made in
methanol/ ethylene glycol as solvent and the solution was degassed
with nitrogen gas for 15 min. This solution was irradiated in quartz test
tube by keeping at different distances. The reaction mixture was col-
lected at different time intervals for GC analysis and the product dis-
tribution was analyzed by gas chromatography.
Fig. 1. Photo flow reactor set up.
time and consistency in outlet composition for a set of conditions when
compared with conventional batch photochemical synthesis. The effect
of viscosity of solvent in the product distribution is explored to arrest
the radical pair movement to modify the isomer ratio. After this brief
Introduction, in the next Section we give details of the experimental set-
up and the experimental procedure. Subsequently, we discuss the re-
sults on conversion and selectivity of the isomers for variety of condi-
tions in detail. Finally we summarize our observations.
2.5. Photo flow reactor
The photo flow reactor design was fabricated by quartz coil tubing
(Length: 2.5 m, ID: 3 mm) around UV- lamp (450 W medium pressure
mercury lamp). This quartz coil tube was equipped with a peristaltic
pump and a polymeric tubing for fluid transfer (Tubing ID: 3.18 mm,
total reactor volume: 50 mL). This quartz coil reactor was covered with
aluminum foil.
2. Experimental section
2.1. General information
Phenyl benzoate was synthesized and characterized by 1H NMR
spectrum in CDCl3 as a solvent. Ortho- and para-hydroxybenzophenones
were obtained by photo-fries rearrangement reaction, then purified it
by column chromatography and characterized by 1H NMR in CDCl3 as a
solvent. For photolysis, phenyl benzoate solution was prepared by
dissolving it in methanol and ethylene glycol (2 mg mL−1). The solution
of phenyl benzoate was irradiated in a quartz tube using a UV source
(450 W medium pressure mercury lamp). The percentage conversion
and product distribution were obtained by analyzing the samples (2 μL
sample having concentration of 1 mg mL−1) with gas chromatography
(Thermo) equipped with flame ionization detector and HP-5 column
packed with nitrogen as a carrier gas. GC method was set such that for
the first 1 min temperature was set at 100 °C beyond which it was in-
creased progressively at a rate of 10 °C/min up to 250 °C and then it was
retained at 250 °C for next 3 min. The data based on calibration (given
in the SI) was used for the estimation of conversion of phenyl benzoate
and selectivity of product isomers.
2.6. General procedure for flow photo-fries rearrangement reaction
Phenyl benzoate solution was made in methanol/ ethylene glycol as
solvent with 10 mM concentration, this solution was pumped through
the coil tube at three different flow rates (3.2 mL min−1, 6.4 mL min−1
and 17.5 mL min−1 respectively). After irradiation, reaction mixture
was collected at different time intervals during photolysis at outlet. In
order to increase the residence time without changing the velocity in
the photochemical tubular reactor, the outlet was connected with the
inlet and the reaction mass was pumped using peristaltic pump con-
tinuously for very long time until it reaches 100% conversion. This
approach helped retain constant superficial velocity in the reactor in-
dependent of monitoring time. The product distribution was analyzed
by gas chromatography.
2.6.1. 2-Hydroxybenzophenone (o-isomer, 1a)
1H NMR (200 MHz, CDCl3) δ: 6.89 (ddd, J = 8.08, 7.14, 1.20 Hz,
1 H), 7.09 (dd, J = 8.08, 0.82 Hz, 1 H), 7.37–7.75 (m, 7 H), 12.06 (s,
1 H).
2.2. Calibration
Solutions of phenyl benzoate, phenol, ortho- and para- hydro-
xybenzophenone in methanol were made by keeping the concentration
of 0.125, 0.25, 0.5 and 1 mg mL−1 and analyzed by gas chromato-
graphy by injecting 2 μL of each sample. The obtained peak area was
2.6.2. 4-Hydroxybenzophenone (p-isomer, 1b)
1H NMR (200 MHz, CDCl3) δ: 6.63 (s, 1 H), 6.87–6.99 (m, 2 H),
7.39–7.64 (m, 3 H), 7.69–7.86 (m, 4 H).
317

N. Karjule et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
Scheme 1. Photo-Fries rearrangement of phenyl benzoate.
3. Results and discussion
Table 1
Effect of distance from the light source and radiation time on conversion and
selectivity of isomers in batch mode (Solvent used: Methanol).
In general, the photo-Fries rearrangement is proposed to follow
radical pair formation from excited singlet state and subsequent re-
arrangement [28,29]. The first mechanism indicates a homolytic clea-
vage of the excited molecule occurring at the ArOeCOR bond (Scheme
1). The resulting pair of radicals would be restrained by a solvent cage
until they are combined to form the rearranged products else the radical
pair would drift apart and the phenoxyl radical would eventually ab-
stract a hydrogen atom to form the respective phenol. Formation of
phenol and perhaps para-rearranged product could occur as a result of a
homolytic cleavage and hydrogen abstraction. According to this me-
chanism processes leading to the formation of phenol or rearranged
products would represent competitive de-excitation pathways. In the
photo-fries rearrangement of phenyl benzoate, the product distribution
observed in homogeneous solution in solvents such as benzene and
methanol can be altered by using cyclodextrin, micelles and zeolites
which helps to enhance the selectivity of ortho-isomer to more than
90% [30–34].
The product distribution can provide the information about the
radical-pair combination that occurs in isotropic solutions. The pro-
ducts obtained from Photo-Fries rearrangement infer the mobility and
diffusivity of radical pair thus formed. Ortho-(1a) and para-(1b) isomers
of rearranged ketones are formed by the mobility of radical pairs
whereas phenol formed by diffusion of phenoxyl radical from the sol-
vent cage. In general, for parallel reactions the product isomer ratio
depends on the rate constants of competitive reactions and the reaction
conditions (viz. temperature, polarity, pH, solvent) [35,36]. In photo-
chemical reactions viscosity of solvent plays a prominent role in de-
ciding the isomer ratio by affecting the translational or rotational re-
arrangement [37]. Also, the polar solvent favours rearrangement and
non-polar solvent favours phenol formation. For example, for tert-bu-
tanol, iso-propanol, ethanol and methanol as solvents the viscosity
decreases from 3.35 m Pa s to 0.56 m Pa s, and with decreasing viscosity
the isomer ratio also decreases from 1.66 to 0.85 [38,39]. Thus, using
solvents with higher viscosity will always tend to support the formation
of ortho-isomer. In order to explore the effect of radiation time, in-
tensity and solvent, a few controlled experiments were carried out in
batch mode. Reaction in methanol and ethylene glycol results in the
ortho- to para-isomers ratio (o-/p-, 1a/1b) between 1.29 to 2.2 and 6.3,
respectively, which correlates well with the viscosity of the solvents,
the observations are shown in Table 1 (Fig. S3-S7) and Table 3.
At a fixed concentration of the substrate (2 mg mL−1) the effect of
Experimental details
Observations
Conc. of Phenyl Distance
Time (h) Temp. in the % Conversion o-/p-
benzoate (mg/
mL)
from lamp
(mm)
quartz test
(−)
tube (oC)
2
2
2
2
200
200
200
20
1
2
3
1
29
30
30
43
40
60
77
92
1.6
1.4
1.3
2.2
distance from the light source was found to be significant. For example,
at a distance of 20 mm and 200 mm from the light source, the % con-
version decreased from 92% to 40% in 1 h, while the corresponding
isomer ratio (o-/p-) decreased from 2.2 to 1.6, respectively (Fig. 2). The
cage escape product, phenol was not observed under the present ex-
perimental conditions. This reduction in the isomer ratio as well as
conversion even after longer exposure to UV light was an effect of the
local temperature. This indicates the lower conversion can be attributed
to the lower intensity of light; the variation in the isomer ratio was due
to the orientation of substitution which depends on the local tem-
perature for these parallel reactions. In general, an increase in tem-
perature increases the rate of a chemical reaction. In the set of these
two parallel reactions, the overall rate constant [k = koe-(E/RT)] for the
reaction favouring o-substitution is higher than that of p-substitution.
This observation is evident from the isomer ratio. Thus, even if the
activation energy for these two parallel reactions might be similar, in-
crease in temperature will always favor the faster reaction, which is o-
substitution. It is observed from these experiments that, after an ex-
posure for 1 h the isomer ratio decreased with increasing distance from
the light source, which supports the effect of temperature [40]. Since
the variation in the isomer ratio at complete conversion of the substrate
was not significantly different, the total volume of substrate can have
effect on the time needed for complete conversion and the corre-
sponding isomer ratio. Such semi-batch mode experiments were per-
formed and are reported in the Supporting Information (SI-3). Such
experiments indicated that the % conversion is independent of the
substrate volume however the temperature inside the vial varies in time
due to continuous addition of one of the reactant and thus can show
different reaction completion times.
At a fixed distance from the light source (200 mm), it was observed
318

N. Karjule et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
Fig. 2. The time history of the effect of distance from the light source on the variation in the conversion and the product isomer ratio at an initial substrate
concentration of 2 mg mL−1 (a) 200 mm and (b) 20 mm from the light source.
that while conversion continues to increase with time, the isomer ratio
o-/p- decreased from 1.57 to 1.29. The temperature inside the vial was
observed to vary slightly in time. However, the product has higher UV
absorbance than the substrate, it is possible that due to reduction in the
photon density available at a given wavelength required for the desired
reaction to take place, the reaction favouring o-isomer would slow
down. In this situation, the isomer ratio o-/p- would continue to de-
crease with time. In view of this, further experiments were carried out
in continuous flow manner using a helical quartz tube (having circular
cross-section) kept around a UV light source. The continuous flow mode
would help achieve consistency in reaction performance due to differ-
ential exposure to the light [41]. Moreover the secondary flow (Dean
flow) generated in the helical coil does not allow the velocity profile to
remain axisymmetric and lowers the extent of dispersion [42], which is
a desirable situation.
Several experiments were carried out by changing the flow rates so
that the effect of residence time on reaction progress can be studied.
The product distribution upon photolysis of the substrates in two dif-
ferent solvent are shown in Fig. 3. The result indicates that the rates of
photo-Fries rearrangement reaction of phenyl benzoate in batch and
continuous flow mode are markedly and can be seen from the reaction
time or residence time in these two modes [43]. The conversion was
higher in flow mode as compared to the batch reaction. As a bench
mark study, initially batch mode experiment was repeated with ethy-
lene glycol as the solvent. In a quartz test-tube placed at 20 mm from
the UV lamp (having same as radius of the quartz coil used for con-
tinuous flow experiments), with methanol as the solvent, complete
conversion was obtained in 40 min while in the flow reactor (quartz
coil), it was achieved in 5 min (Fig. 3a). Also, the isomer ratio for the
continuous mode remained almost constant (1.68–1.73) for all the re-
sidence times investigated. Since the isomer ratio is also an effect of the
rate at which the movement of functional groups (or radial pairs)
happens in this case, the rate of this movement can be modified by
using solvents of different viscosities.
It was observed that with methanol as solvent, the o-/p- ratio ob-
tained from batch and flow reactor (17.6 mL min−1) did not change
noticeably implying that the molecular level changes did not vary much
depending upon the mode of operation. In ethylene glycol as solvent,
the selectivity for o-isomer was more as compared to methanol (Fig. S7-
S10). The physical properties of both the solvents are given in Table 2.
The complete conversion of the substrate was found to occur 12 times
faster in quartz coil with ethylene glycol as solvent as compared to a
batch. Solvents with higher viscosity were found to restrict 1,5-shift of
radical pair, which reduces the selectivity of p-isomer. However higher
viscosity also reduces the intensity of photo penetration in the reaction
mass and thus needs longer reaction time to achieve 100% conversion.
In order to study the effect of flow rate to the o-/p- ratio of the
products, experiments were carried out with 3.2 mL min−1 (0.0075 m/
s), 6.4 mL min−1 (0.0151 m/s) and 17.6 mL min−1 (0.0415 m/s) flow
rates in methanol and ethylene glycol, independently as solvents
(Table 3). At lower flow rates, the reaction was seen to be faster due to
relatively longer exposure of light. In case of methanol as solvent, there
was no change in o-/p- product ratio with increase in residence time;
however the reaction rate was higher. With ethylene glycol, o-/p-
isomer ratio was relatively higher which decreased with increasing flow
rate (less residence time). There was significant improvement in the o-/
p- ratio (by 8 folds) with ethylene glycol as the solvent when compared
to methanol. The changes in the o-/p- product ratio with respect to
Fig. 3. Relative differences in the conversion and isomer ratio from batch and continuous flow (flow rate of 17.6 mL min−1) photochemical reaction in specific
solvents: (a) Methanol (MeOH) (b) Ethylene glycol (EG).
319

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JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
4. Conclusion
Table 2
Comparison between solvent system and product distribution.
We have studied the reactivity of the singlet radical pair in Photo-
Fries rearrangement of phenyl benzoate in continuous flow synthesis by
using solvents of different viscosities and shear rates. The observations
from batch mode experiments indicated that the local rise in tem-
perature in the reaction media due to longer exposure to radiation
changes the reaction rates over the time and also the viscosity of media,
together affects the isomer ratio. In the semi-batch mode of experi-
ments, the % conversion is independent of the substrate volume and the
% conversion can be controlled by prolonged addition of the substrate
by controlling the temperature. In continuous flow, there is a significant
reduction in reaction time. The o-/p- isomer ratio can be increased by
using a solvent of higher viscosity as well as confined domain. Ethylene
glycol as solvent yields high ortho-regioselectivity as compared to me-
thanol. We have observed significant changes in the o-/p- product ratio
with respect to residence time. The work is being extended for variety
of other systems involving radical pairs.
Solvent
Viscosity
(Pa s)
Method
Time
(min)
Conversion
(%)
o-/p-
Methanol
5.9 × 10−4
1.6 × 10−2
Batch
Continuous
Batch
40
5
180
10
92
2.2
100
100
100
1.68
6.28
2.72
Ethylene glycol
Continuous
Table 3
Effect of velocity in the helical coil on the isomer yield and isomer ratio in
presence of ethylene glycol and methanol as solvents. In all the runs the con-
version at the outlet was 100%.
Superficial velocity
(m/s)
Methanol
Ethylene glycol
Residence time
(min)
o-/p- Residence time
o-/p-
(min)
0.0075
0.0151
0.0415
11.13
11.16
5
1.51
1.61
1.68
42.6
21.3
10
12.4
7.01
2.72
Acknowledgments
Neeta Karjule thanks UGC for fellowship. Mrityunjay K. Sharma
thanks CSIR-SRF for fellowship. All authors thankfully acknowledge the
financial support from Indus Magic Program of CSIRs.
Table 4
Reaction in ethylene glycol and glycerol mixture.
Method
Solvent
Ethylene glycol : (Pa.s)
glycerol
Viscosity Residence time
Conversion o-/p-
(%)
Appendix A. Supplementary data
(min)
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.jphotochem.2018.06.
014.
Batch
Continuous 4:1
Continuous 1.5:1
4:1
0.236
0.236
0.481
180
5.2
6.6
88.9
100
100
4.4
8.45
8.14
References
residence time indicated that the geminate radical pair thus formed was
in tight solvent cage. At longer residence time radical pairs showed
lower mobility resulting in the formation of more o-isomer and hence
higher o-/p- isomer ratio [Table 3, Fig. S11-S12, S8 (For MeOH), and
S13-S14, S10 (For ethylene glycol)]. It is recommended to have higher
flow rates as it helps achieve thinner boundary layer near the tube wall
thereby helping better photon penetration, however higher conversion
needs longer residence time. These two effects can be brought into ef-
fect either by having longer tube or by recirculating the reaction mass
through the tube, making it almost like a vigorously stirred batch re-
actor having very high shear rate.
[1] R.G. Weiss, V. Ramamurthy, G.S. Hammond, Photochemistry in organized and
confining media: a model, Acc. Chem. Res. 26 (1993) 530–536.
[2] V. Ramamurthy, Photochemistry in Organized and Constrained media, VCH, New
York, 1991.
[3] K. Pitchumani, M. Warrier, V. Ramamurthy, Remarkable product selectivity during
photo-fries and photo-claisen rearrangements within zeolites, J. Am. Chem. Soc.
118 (1996) 9428–9429.
[4] C.S. Cundy, R. Higgins, S.A.M. Kibby, B.M. Lowe, R.M. Paton, Para-selective fries
rearrangement of phenyl acetate in the presence of zeolite molecular sieves,
Tetrahedron Lett. 30 (1989) 2281–2284.
[5] D. Andrew, B.T. Des Islet, A. Margaritis, A.C. Weedon, Photo-fries rearrangement of
naphthyl acetate in supercritical carbon dioxide: chemical evidence for solvent-
solute clustering, J. Am. Chem. Soc. 117 (1995) 6132–6133.
[6] M.R. Sandner, E. Hedaya, D.J. Trecker, Mechanistic studies of the photo-Fries re-
action, J. Am. Chem. Soc. 90 (1968) 7249–7254.
The effect of viscosity was further investigated by using mixture of
ethylene glycol and glycerol mixtures as solvents (Table 4, Fig. S15-
S17). The addition of 20% and 40% of glycerol to ethylene glycol in-
creased the viscosity of reaction media by 2 times, which enhanced the
reaction rate by 22% with less than 3.6% variation in the isomer ratio.
The reaction under consideration is a fast geminate reaction in the
solvent cage that provides the o-isomer. In general the high o-/p- ratio
of rearranged products can be obtained by (i) confinement of geminate
radical pair thus formed by laminar or turbulent flow which is not the
case as the width of the flow reactor (in mm) is really huge compared to
that of the dimensions of present the molecular system in a solvent cage
(few nm) or (ii) by changing the change viscosity, as viscous medium
restricts the motion of radical pair to form more o- isomer, which can be
realized by the possibility of presence of gradient of viscous regions in
the flow reactor in the given solvent system which is responsible for the
observation of such high o-/p- ratio of products. We feel that the var-
iation in the shear rate of the reaction media in the vicinity of the tube
wall make a difference by causing difference in the motion of radical
pair. A lot more data over a wide range of viscosity would help to get
better insights on such systems and it will be studied separately.
[7] C.E. Kalmus, D.M. Hercules, A mechanistic study of the photo-Fries rearrangement
of phenyl acetate, J. Am. Chem. Soc. 96 (1974) 449–456.
[8] V. Ramamurthy, K.S. Schanze, Photochemistry of Organic Molecules in Isotropic
and Anisotropic Media vol. 9, (2003).
[9] M. Oelgemöller, O. Shvydkiv, Recent advances in microflow photochemistry,
Molecules 16 (2011) 7522–7550.
[10] R.L. Hartman, K.F. Jensen, Microchemical systems for continuous-flow synthesis,
Lab Chip 9 (2009) 2495–2507.
[11] M. Oelgemöeller, Highlights of photochemical reactions in microflow reactors,
Chem. Eng. Technol. 35 (2012) 1144–1152.
[12] T. Noël, A personal perspective on the future of flow photochemistry, J. Flow.
Chem. 7 (2017) 87–93.
[13] I.R. Baxendale, The integration of flow reactors into synthetic organic chemistry, J.
Chem. Technol. Biotechnol. 88 (2013) 519–552.
[14] K. Terao, Y. Nishiyama, S. Aida, H. Tanimoto, T. Morimoto, K. Kakiuchi, Diastereo-
differentiating [2+2] photocycloaddition of chiral cyclohexenone carboxylates
with cyclopentene by a microreactor, J. Photochem. Photobiol. Sci. A: Chem. 242
(2012) 13–19.
[15] H. Lu, M.A. Schmidt, K.F. Jensen, Photochemical reactions and on-line UV detection
in microfabricated reactors, Lab Chip 1 (2001) 22–28.
[16] K. Pimparkar, B. Yen, J.R. Goodell, V.I. Martin, W.-H. Lee, J.A. Porco, A.B. Beeler,
K.F. Jensen, Development of a photochemical microfluidics platform, J. Flow.
Chem. 2 (2011) 53–55.
[17] J.P. Knowles, L.D. Elliott, K.I. Booker-Milburn, Flow photochemistry: Old light
through new windows, Beilstein J. Nanotechnol. 8 (2012) 2025–2052.
[18] Y. Su, N.J.W. Straathof, V. Hessel, T. Noël, Photochemical transformations ac-
celerated in continuous-flow reactors: basic concepts and applications, Chem. Eur.
320

N. Karjule et al.
JournalofPhotochemistry&PhotobiologyA:Chemistry364(2018)316–321
vs photodecarboxylation—substituent and solvent effects, Tetrahedron 25 (1969)
6015–6024.
J. 20 (2014) 10562–10589.
[19] F.R. Bou-Hamdan, F. Lévesque, A.G. O’Brien, P.H. Seeberger, Continuous flow
photolysis of aryl azides: preparation of 3H-azepinones, Beilstein J. Nanotechnol. 7
(2011) 1124–1129.
[20] S. Fuse, Y. Mifune, N. Tanabe, T. Takahashi, Continuous-flow synthesis of activated
vitamin D3 and its analogues, Org. Biomol. Chem. 10 (2012) 5205–5211.
[21] H. Maeda, H. Mukae, K. Mizuno, Enhanced efficiency and regioselectivity of in-
tramolecular (2π+2π) photocycloaddition of 1-cyanonaphthalene derivative using
microreactors, Chem. Lett. 34 (2005) 66–67.
[22] E. Shahbazali, T. Noël, V. Hessel, Photo-claisen rearrangement of allyl phenyl ether
in microflow: influence of phenyl core substituents and vision on orthogonality, J.
Flow. Chem. 6 (2016) 252–259.
[23] F. Lévesque, P.H. Seeberger, Continuous-flow synthesis of the anti-malaria drug
artemisinin, Angew. Chem. Int. Ed. 51 (2012) 1706-1079.
[31] G.M. Coppinger, E.R. Bell, Photo-Fries rearrangement of aromatic esters. Role of
steric and electronic factors, J. Phys.Chem. 70 (1966) 3479–3489.
[32] H.S. Banu, K. Pitchumani, C. Srinivasan, Effect of cyclodextrin complexation on
photo-Fries rearrangement of naphthyl esters, Tetrahedron 55 (1999) 9601–9610.
[33] A.K. Singh, S.M. Sonar, Photorearrangement of aryl esters in micellar medium,
Synth. Comm. 15 (1985) 1113–1121.
[34] W. Gu, M. Warrier, V. Ramamurthy, R.G. Weiss, Photo-Fries reactions of 1-naphthyl
esters in cation-exchanged zeolite Y and polyethylene media, J. Am. Chem. Soc. 121
(1999) 9467–9468.
[35] M.J.S. Dewar, L.S. Hart, Aromatic rearrangements in the benzene series—I: the fries
rearrangement of phenyl benzoate: the benzoylation of phenol, Tetrahedron 26
(1970) 973–1000.
[24] E. Lobry, F. Jasinski, M. Penconi, A. Chemtob, C. Croutxé-Barghorn, E. Oliveros,
A.M. Braun, A. Criqui, Continuous-flow synthesis of polymer nanoparticles in a
microreactor viaminiemulsion photopolymerization, RSC Adv. 4 (2014)
43756–43759.
[25] M.G. Hernández-Linares, G. Guerrero-Luna, S. Pérez-Estrada, M. Ellison,
M.–M. Ortin, M.A. Garcia-Garibay, Large-scale Green chemical synthesis of adjacent
quaternary chiral centers by continuous flow photodecarbonylation of aqueous
suspensions of nanocrystalline ketones, J. Am. Chem. Soc. 137 (2015) 1679–1684.
[26] M. Baumann, I.R. Baxendale, Continuous photochemistry: the flow synthesis of
ibuprofen via a photo-Favorskii rearrangement, React. Chem. Eng. 1 (2016)
147–150.
[27] F. Lévesque, P.H. Seeberger, Highly efficient continuous flow Reactions using
singlet oxygen as a “Green” reagent, Org. Lett. 13 (2011) 5008–5011.
[28] T. Arai, S. Tobita, H. Shizuka, Direct measurements of the rates of 1,3- and 1,5-
sigmatropic hydrogen shifts in the photo-Fries rearrangements of phenyl acetate,
Chem. Phys. Lett. 223 (1994) 521–526.
[29] N.M. Cullinane, B.F.R. Edwards, The Fries rearrangement. Part V. Effect of the ring
substituent and the acyl group, J. Chem. Soc. (1958) 2926–2929.
[30] H.J. Hageman, The photoreactions of some aryl esters : photo-Fries rearrangement
[36] D. Belluč, P. Hrdlovič, Photochemical rearrangement of aryl, vinyl, and substituted
vinyl esters and amides of carboxylic acids, Chem. Rev. 67 (1967) 599–609.
[37] R. Suau, G. Torres, M. Valpuesta, The photo-fries rearrangement of 2, 5-dis-
ubstituted phenyl acetates, Tetrahedron Lett. 36 (1995) 1311–1314.
[38] D.A. Plank, The photo-Fries reaction of aryl esters: effect of solvent on production
distribution, Tetrahedron Lett. 9 (1968) 5423–5426.
[39] M.S. Syamala, V. Ramamurthy, Modification of photochemical reactivity by cy-
clodextrin complexation: selectivity in photo-claisen rearrangement, Tetrahedron
44 (1988) 7223–7233.
[40] J. Xu, R.G. Weiss, Analyses of in-cage singlet radical-pair motions from irradiations
of 1-naphthyl (R)-1-phenylethyl ether and 1-naphthyl (R)-2-phenylpropanoate in n-
alkanes, J. Org. Chem. 70 (2005) 1243–1252.
[41] D. Cambié, C. Bottecchia, N.J.W. Straathof, V. Hessel, T. Noël, Applications of
continuous- flow photochemistry in organic synthesis material science, and water
treatment, Chem. Rev. 116 (2016) 10276–10341.
[42] S. Vashisth, V. Kumar, K.D.P. Nigam, A review on the potential applications of
curved geometries in process industry, Ind. Eng. Chem. Res. 47 (2008) 3291–3337.
[43] K. Gilmore, P.H. Seeberger, Continuous flow photochemistry, Chem. Rec. 14 (2014)
410–418.
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