Photocatalytic activation of N-chloro compounds for the chlorination of arenes

Article abstract of DOI:10.1016/j.tet.2016.06.028

Photoredox catalysis activates N-chloramines and N-chloro-succinimide (NCS) for the electrophilic chlorination of arenes. The photooxidation of the nitrogen atom to a radical cation induces a positive polarization on the chlorine atom, which results in a higher reactivity in electrophilic aromatic chlorination reactions.

Full text of DOI:10.1016/j.tet.2016.06.028

Tetrahedron xxx (2016) 1e5
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Photocatalytic activation of N-chloro compounds for the
chlorination of arenes
Thea Hering, Burkhard K o€ nig *
University of Regensburg, Faculty of Chemistry and Pharmacy, D-93040 Regensburg, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Photoredox catalysis activates N-chloramines and N-chloro-succinimide (NCS) for the electrophilic
chlorination of arenes. The photooxidation of the nitrogen atom to a radical cation induces a positive
polarization on the chlorine atom, which results in a higher reactivity in electrophilic aromatic chlori-
nation reactions.
Received 28 April 2016
Received in revised form 2 June 2016
Accepted 8 June 2016
Available online xxx
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Photocatalysis
Electron transfer
Electrophilic chlorination
1. Introduction
the nitrogen atom to a radical cation 2 as depicted in Scheme 1. The
resulting radical cation 2 has a significantly enhanced reactivity
Chlorinated aromatic compounds can be found in many phar-
maceuticals, agrochemicals, and polymers and serve as starting
materials for the synthesis of organometallic reagents. Moreover,
they are versatile synthetic precursors for metal catalyzed cross-
couplings.1 Due to the importance of aromatic chlorides the de-
velopment of efficient strategies for the electrophilic chlorination
of arenes under mild conditions is still of great interest. Since
chloride usually does not undergo electrophilic aromatic sub-
stitution, but rather reacts as a nucleophile these transformations
compared to the neutral N-chloro compound 1 since the positive
charge on the nitrogen pulls electron density from the chlorine and
induces a strong positive polarization (
d
þ). This cation radical 2
contains an electrophilic chlorine atom and can react in an elec-
trophilic aromatic substitution with suitable arenes to give chlori-
nated compounds 4 (Scheme 1).
e4
þ
require the use of a ‘Cl ’ reagent. Traditional electrophilic chlori-
t
nation reagents as Cl
are also rather unselective.
2
, SO
2
Cl
2
and BuOCl have a high reactivity, but
1
,5,6
Their hazardous properties make
them difficult to handle and limit practical applications. N-Chloro
compounds, such as N-chlorosuccinimide (NCS), N-chloramines or
modern guanidine based reagents (Palau’chlor) are valuable al-
7
Scheme 1. General scheme of the oxidative activation of N-chloro compounds by
photoredox catalysis (PC¼photocatalyst).
ternatives as they contain positively polarized chlorine atoms and
are inexpensive and easy to handle. However, except for Palau’-
chlor, which requires a multi-step synthesis, they show only
moderate reactivity and often need activation by redox active
The use of photoredox catalysis to oxidize 1 would offer a mild
way to catalytically activate N-chloramines/-amides by visible light
at room temperature. This strategy offers a practical alternative to
conventional activation pathways.
metals,8
e10
Lewis
11e13
or Brønsted acids
14,15
or radical initiators.
16
Most of these activations rely on an increase of the NꢀCl bond
polarization by decreasing the electron density on the nitrogen,
e.g., by coordination of a Lewis acid or protonation of the nitrogen.
An analogous effect can be achieved by photocatalytic oxidation of
2. Results and discussion
There are few reports known using N-chloramines as starting
materials in photoredox catalysis. However, these examples are not
based on the oxidation of N-chloramines to activate them for
*
Corresponding author. Tel.: þ49 941 943 4575; fax: þ49 941 943 1717; e-mail
address: burkhard.koenig@ur.de (B. K o€ nig).
http://dx.doi.org/10.1016/j.tet.2016.06.028
0
040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hering, T.; K o€ nig, B., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.06.028

2
T. Hering, B. K o€ nig / Tetrahedron xxx (2016) 1e5
electrophilic chlorination, but rather on the reduction to induce
The N-chloro compounds with benzyl groups 1c and with ‘push-
pull’ substituents 1d (entries 3, 4) gave comparable yields,
but are unfavourable with respect to atom economy. Further opti-
mization of the reaction was therefore carried out using 1-
chloromorpholine (1b).
Having identified the suitable N-chloramine, we continued with
varying the solvent of the reaction (Table 2). All polar solvents and
DCM (entries 1e4) showed conversion to the desired product 4b,
whereas the non-polar solvents toluene and 1,2-dichloroethane
(1,2-DCE) gave only minor product formation (entries 5, 6). This
observation can be explained by the different solubility of the
photocatalyst, which poorly dissolves in non-polar solvents. The
reaction was most efficient in a mixture of MeCN and water (entry
4), which even led to double chlorination. The enhanced reactivity
when water is added to the reaction presumably results from
a higher solubility of peroxodisulfate ensuring a quicker re-
generation of the photocatalyst.
ꢀ
a cleavage of Cl yielding a nitrogen atom centered radical, which
reacts further to form a CeN-bond.17,18 Even though in some ex-
amples chloride is later incorporated into the product, it always
reacts as a nucleophile and not as an electrophile. To investigate
whether N-chloramines (1) can also be activated by photocatalytic
E
oxidation to undergo electrophilic aromatic substitution (S Ar), we
chose the chlorination of an electron rich arene, namely dime-
thoxybenzene (3a) as a model reaction (Scheme 2): A solution of 3a
(
[
0.25 mmol), the N-chloramine 1a (1.2 equiv), the photocatalyst
Ru(bpy) ]Cl (5 mol %) and ammonium peroxodisulfate (1.2 equiv)
3
2
to reoxidize the photocatalyst in MeCN was irradiated under N
2
-
atmosphere over night with blue LEDs (
tocatalytic reaction yielded 13% of the chlorinated arene 4a
l
max¼455 nm). The pho-
whereas without irradiation no chlorination was observed.
For further studies the substrate was changed from dimethox-
ybenzene (3a) to the less electron rich anisole (3b) since this will
circumvent the problem of double chlorination. Table 3 summa-
rizes the results of the reaction optimization. First, we continued
the solvent screening and tested different MeCN/H
2
O ratios (Table
Scheme 2. Test reaction for the photocatalytic chlorination of dimethoxybenzene (3a)
with 1-chlororpiperidine (1a).
3, entries 1e3). The reaction using a 4:1 mixture of MeCN and
2
H O showed an excellent yield of 95%. Using this solvent mixture
the catalyst loading could be lowered to 2 mol % without a change
in the yield. A further decrease to 1 mol % showed a slightly de-
creased yield of 80% (entries 2, 4, 5). Neither the addition of base
Even though the yield of chlorination was low, these initial re-
sults showed that N-chloramines can be activated for S Ar by
E
photocatalytic oxidation. Next, the reaction conditions were opti-
mized. First we investigated whether the metal based photocatalyst
Table 1
[
Ru(bpy)
3
]Cl
2
can be replaced by cheap organic dyes such as eosin Y
Variation of the N-chloro compound using the reaction conditions depicted in
þ
or 9-mesityl-10-methylacridinium perchlorate (Acr eMes)
Scheme 2
a
0
ꢁ
(
Scheme 3). The redox properties of eosin Y (E (EY*/EY ꢀ)¼0.79 V vs
Entry
N-chloro compound
Yield (%)b
13
Conversion (%)b
26
0 19
SCE) are similar to [Ru(bpy)
3
]Cl
2
(E (Ru(II)*/Ru(I))¼0.77 V vs SCE),
nevertheless only traces of chlorination could be obtained when
using 10 mol % eosin Y instead of [Ru(bpy)
3
]Cl
2
(yield 4a<5%). Next
1
2
3
þ
we tested Acr eMes, which is a very strong oxidant in its excited
state (E0(MAþ*/MA )¼2.08 V vs SCE), but despite this high oxidative
ꢁ
20
power the catalyst was less efficient in this transformation than
74
>99
>99
[
3 2
Ru(bpy) ]Cl (yield 4a 7%). A possible complication with this cat-
alyst could be that its oxidation potential is sufficiently high to
oxidize dimethoxybenzene (3a) directly and thus leads to un-
desired side reactions.21
62
4
61
>99
a
Reactions were carried out using 0.25 mmol 3a, 1.2 equiv of the respective N-
, and 5 mol % [Ru(bpy) ]Cl O in 1.5 mL
ꢂ6H
max¼455 nm) was 16 h.
Determined by GC analysis using anisole as the internal standard.
chloro compound, 1.2 equiv (NH
MeCN. The irradiation time (
4
)
2
S
2
O
8
3
2
2
l
b
Scheme 3. Employed photocatalyst and the wavelength used for irradiation.
Table 2
Results of the solvent screening
a
Entry
Solvent
Yield (%)b
Conversion (%)b
Next, we varied the N-chloramine to investigate the influence of
the substituents on the nitrogen. The results of this screening are
depicted in Table 1. The highest yields of chlorinated dimethox-
ybenzene 4a were obtained using 1-chloromorpholine (1b) (74%,
entry 2), which is except for the heteroatom structurally very similar
1
2
3
4
5
6
MeCN
MeOH
DCM
MeCN/H
Toluene
1,2-DCE
74
42
45
>99
60
45
>99
<5
22
c
2
O 3:1
48þDC
<5
7
y
to the previously employed piperidine derivative (1a, entry 1).
a
Reactions were carried out using 0.25 mmol 3a, 1.2 equiv 1b, 1.2 equiv
, and 5 mol % [Ru(bpy) ]Cl O in 1.5 mL of the respective solvent.
ꢂ6H
The irradiation time (
(
NH
4
)
2
S
2
O
8
3
2
2
l
max¼455 nm) was 16 h.
y
b
In reported aromatic chlorinations with N-chloramines the morpholine de-
Determined by GC analysis using anisole as the internal standard.
c
rivative showed higher efficiency than N-chloropiperidine, see Ref. 14.
DC¼double chlorination.
Please cite this article in press as: Hering, T.; K o€ nig, B., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.06.028

T. Hering, B. K o€ nig / Tetrahedron xxx (2016) 1e5
3
Table 3
Table 4
Reaction optimization with anisole (3b) as the substrate
Scope of the visible light mediated chlorination of arenes with N-chloraminesa
Conversion (%)b
95
Yield (%)b
95
Selectivity (p:o)
5:1
Entry
Reaction condition
Yield (%)a
p:o ratio)
Conv. (%)a
Entry
1
Substrate
(
1b
5 mol % Ru(bpy)
5 mol % Ru(bpy)
5 mol % Ru(bpy)
2 mol % Ru(bpy)
1 mol % Ru(bpy)
5 mol % Ru(bpy)
5 mol % Ru(bpy)
5 mol % Ru(bpy)
5 mol % Ru(bpy)
, MeCN
26 (11:1)
88 (5:1)
95 (5:1)
90 (5:1)
80 (5:1)
70 (6:1)
13 (5:1)
76 (6:1)
76 (5:1)
46
>99
95
90
83
83
32
88
>99
3
Cl
3
Cl
3
Cl
3
Cl
3
Cl
3
Cl
3
Cl
3
Cl
3
Cl
2
2
2
2
2
2
2
2
2
b
2
, MeCN/H
, MeCN/H
, MeCN/H
, MeCN/H
, MeCN, NaOAc
, MeCN, pyridine
, MeCN, HCl 2 M
2
2
2
2
O 9:1
O 4:1
O 9:1
O 9:1
3
4
5
b
b
2c
>99
74
100:0
6
7
8
9
, MeCN/H
2
O 9:1,
2
equiv 1b
5 mol % Ru(bpy)
no (NH
No Ru(bpy)
3d
100
55
66
41
75
2:1
1
0
3
Cl
2
, MeCN/H
2
O 9:1,
0
0
4 2 2 8
) S O
1
1
1
2
3
Cl
2
, MeCN/H
2
O 9:1
O 9:1,
27 (4:1)
18 (3:1)
48
33
4
5
13:1
2:1
5 mol % Ru(bpy)
no light
3
Cl , MeCN/H
2
2
a
Determined by GC analysis using toluene as the internal standard.
Average over two reactions.
b
83
(
entries 6, 7) nor acid (entry 8) or a higher amount of the N-chlo-
6
100
39
1:1
ramine 1b (entry 9) improved the yield further. The conducted
control reactions (entries 10e12) showed that no efficient reaction
is observed without light, without the catalyst or without
7
8
9
20
24
23
0
20
9
100:0e
2:1f
d
(
NH
reaction without light and without the catalyst (entries 11, 12) in-
dicate that (NH is to some extend able to oxidize the N-
4
)
2
S
2
O
8, respectively. Low amounts of product obtained in the
4 2 2 8
) S O
chloramine 1b. The N-chloro compound 1b itself cannot chlorinate
anisole directly (entry 10).
Having optimized the reaction conditions, we explored the
scope of the reaction towards different arenes (Table 4). Electron
rich substrates with a þM-substituent such as anisole, dimethox-
ybenzene, phenol and acetanilide can be chlorinated in good yields
<5
0
10
d
(
entries 1e5). The aromatic amine 3f (entry 6) showed only
a moderate yield of 39%. The chlorination yield is probably di-
minished by an unproductive direct oxidation of the amine by the
2
2
excited photocatalyst. Unfortunately, the reaction is limited to
electron rich arenes with þM-substituents, arenes with þI-sub-
stituents such as xylene and toluene gave only little chlorinated
product (entries 8, 9). No chlorination could be observed for more
electron poor substrates as chlorobenzene (entry 10). This suggests
that the polarization of the NeCl-bond induced by photocatalytic
oxidation of the nitrogen atom is not strong enough to obtain
highly electrophilic chlorine. Hence, the reaction only proceeds
with very electron rich substrates. Furthermore, we tried to use the
1
1
14
<5
d
a
Reactions were carried out using 0.25 mmol of the arene 3, 1.2 equiv 1b,
, and 2 mol % [Ru(bpy) ]Cl O in 1.5 mL MeCN/H O 4:1.
ꢂ6H
The irradiation time (
max¼455 nm) was 16 h.
1
.2 equiv (NH
4
)
2
S
2
O
8
3
2
2
2
l
b
Determined by GC analysis.
In MeCN.
3 mL solvent.
1-Chloronaphthalene.
2
c
d
e
f
-Chloroxylene: a-chloroxylene.
developed method for the
could only detect traces of chloroacetophenone (entry 11).
a
-chlorination of acetophenone, but
z
N-Chlorosuccinimide (NCS) is a well-known and widely used
chlorination reagent; it generally requires activation. The electron
density on the nitrogen atom is significantly reduced by two elec-
tron withdrawing groups compared to N-chloramines. Accordingly,
the chlorine atom on NCS is more electrophilic leading to a higher
reactivity in S Ar. With photocatalytically activated NCS it should
E
therefore be possible to chlorinate also less electron rich substrates
as xylene and toluene, which were not accessible by N-
chloramines. On the other hand, the electron withdrawing groups
make the oxidative activation of NCS more challenging as they in-
crease the oxidation potential significantly. To investigate whether
the oxidation potential is still within the range of the photocatalyst
[
Ru(bpy)
3
]Cl
2
,
cyclic voltammetry was measured (see
Supplementary data). The obtained potential for the oxidation of
NCS of 1.10 V versus SCE would be too high for an oxidation from
the excited state of the photocatalyst (Scheme 4) as proposed in the
previous paragraph for N-chloramines. However, the potential of
Ru(III), which can be accessed by oxidative quenching of the excited
catalyst Ru(II)* would be sufficient to perform the oxidation of NCS.
z
A reaction with alkenes to obtain aminochlorination by incorporation of the
2
3
Ru(II)* can be oxidized to Ru(III) by (NH
4
)
2
2
S O
8
,
which was also
chlorine as well as the morpholine part was not successful as mainly chlorohydrins
were observed.
employed in the reactions with N-chloramines to re-oxidize Ru(I).
Please cite this article in press as: Hering, T.; K o€ nig, B., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.06.028

4
T. Hering, B. K o€ nig / Tetrahedron xxx (2016) 1e5
significantly enhanced by photoredox catalysis, we next aimed to
explore the effect on a variety of different arenes. To quantify the
effect we compared theyields of chlorination obtained with just NCS
totheyields obtainedusing the photocatalytic activation. The results
are compiled in Table 5. For almost all tested arenes the photo-
catalytic system enabled reactions, which failed to deliver any no-
table amount of product in the absence of the photocatalyst under
the tested reaction conditions. Only for aromatic amines or amides
(entries 7, 8) the reactivity of NCS could not be increased. Xylene and
toluene, which were inaccessible using N-chloramines can be
chlorinated as well (entries 5, 6). The yields are, however, moderate.
3 2
Scheme 4. Redox properties of the photocatalyst [Ru(bpy) ]Cl and oxidation potential
of NCS. Potentials are given versus SCE.23
Based on the redox potentials it is likely that the previously
described photocatalytic activation of the easily oxidizable N-
chloramines proceeds via the reductive quenching of Ru(II)* (re-
ductive quenching cycle) while the more challenging oxidation of
NCS has to proceed via the oxidative quenching cycle where Ru(II)*
3. Conclusion
In conclusion we demonstrated the applicability of visible light
photoredox catalysis to activate N-chloramines and NCS for elec-
trophilic aromatic chlorination of arenes. The activation proceeds
as proposed by oxidation of the nitrogen atom of the N-chloro
compound inducing a positive polarization on the chlorine atom.
The method was applied for the chlorination of a variety of electron
rich arenes. While a þM substituent on the aromatic substrate was
necessary to observe chlorination with the N-chloramine, the
stronger chlorination reagent NCS also allowed the use of less
4 2 2 8
is first quenched by (NH ) S O to give the strongly oxidizing
Ru(III). From a thermodynamic point the photocatalytic activation
of NCS by the developed system is therefore feasible. This would be,
to the best of our knowledge, the first photocatalytic activation of
N
NCS for S Ar. Cho et al. recently reported visible light mediated in
2
4
situ formation of acid chlorides using NCS as a reagent. However,
this reaction proceeds via the transfer of a chlorine radical to
a photocatalytically formed acyl radical and does not involve a di-
rect interaction of the photocatalyst and NCS.
Table 5
Comparison of the electrophilic chlorination using NCS with and without photo-
catalytic activation
To test whether the developed reaction conditions indeed lead
to an enhanced activity of NCS for electrophilic chlorination of
arenes, we monitored the reaction of NCS with anisole with and
without the activation by photoredox catalysis over a period of
a
Entry
Substrate
Conv. (%)b Yield (%)b,c Selectivity NCS, no
a,d
(p:o)
photocat. (%)
1
80 min. The results are summarized in Fig.1. For the photocatalytic
reaction a solution of anisole (3b), NCS (5, 1.2 equiv), (NH
1.2 equiv) and 2 mol % of the photocatalyst in 2 mL MeCN/water
:1 was irradiated with 455 nm under N -atmosphere. Samples
4 2 2 8
) S O
1
2
100
96
92
69
100:0
100:0
<5
(
4
2
were taken after 30 min, 75 min, 120 min and 180 min. For com-
8 (57)
parison a parallel reaction with only anisole (3b) and NCS
(
1.2 equiv) in 2 mL MeCN/water 4:1 was performed and samples
were taken at the same time intervals. Fig. 1 shows a clear en-
hancement of the chlorination yield in the photocatalytic reaction
3
4
5
6
7
58
100
85
79
44
59
38
21
14:1
100:0e
6:1f
0
(
blue curve) compared to the non-catalyzed reaction (red curve).
Thereby we could show that NCS is activated for electrophilic
chlorination by photocatalytic oxidation at room temperature.
As it has been successfully demonstrated that the reactivity of
NCS in the electrophilic aromatic chlorination of anisole is
<1
0
29
1:1
0
100
1:1
44 (44)
8
93
13
25
2:1
23 (25)
9
<5
d
0
a
Photocatalytic reactions were carried out using 0.25 mmol of substrate,
and 2 mol % [Ru(bpy) ]Cl in 1.5 mL solvent
atmosphere. The reactions were irradiated for 16 h.
Determined by quantitative GC analysis using an internal standard.
Yields based on conversion.
1
.2 equiv NCS, 1.2 equiv (NH
4
)
2
S
2
O
8
3
2
under N
2
b
c
d
e
f
Yields in brackets are based on conversion.
1-Chloronaphthalene.
Fig. 1. Monitoring of the chlorination of anisole (3b) by NCS without any activation
2
-Chloroxylene: -chloroxylene.
a
(
red curve) and using the photocatalytic activation shown above (blue curve).
Please cite this article in press as: Hering, T.; K o€ nig, B., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.06.028

T. Hering, B. K o€ nig / Tetrahedron xxx (2016) 1e5
5
electron rich substrates as xylene and toluene. The photocatalytic
activation can serve as a valuable catalytic alternative to conven-
tional activations; the spatial resolution of light activation may be
beneficial for some applications, e.g., in surface science. Using
a similar concept for the activation of other oxidizable reagents in
organic synthesis may be envisaged.
pentadecane) was added to the reaction and the reaction was im-
mediately quenched with satd Na CO -solution and brine. The
mixture was extracted with ethyl acetate and subjected to GCeFID
2
3
analysis.
Acknowledgements
4
4
. Experimental section
We gratefully acknowledge financial support by the Deutsche
Forschungsgemeinschaft (DFG), GRK 1626. T.H. thanks the Fonds
der Deutschen Chemischen Industrie for a fellowship.
.1. General
Photocatalytic reactions were performed with 455 nm LEDs
(
3
OSRAM Oslon SSL 80 royal-blue LEDs,
lem¼455 nm (ꢃ15 nm),
Supplementary data
.5 V, 700 mA). Reaction vials (5 mL crimp cap vials) were illumi-
nated from the bottom with LEDs and cooled from the side using
custom made aluminum cooling block connected to a thermostat.
NMR spectroscopy was carried out on either a Bruker Avance 400
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.06.028.
1
1
13
(
(
(
H: 400.13 MHz, C: 101 MHz, T¼300 K) or a Bruker Avance 300
References and notes
13
H: 300.13 MHz, C: 75 MHz, T¼295 K). The solvent residual peak
d
(CDCl
3
): H 7.26; C 77.0) was used as an internal reference.
1. Fauvarque, J. Pure Appl. Chem. 1996, 68, 1713e1720.
2
3
4
. Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176e4211.
. Gribble, G. W. J. Chem. Educ. 2004, 81, 1441e1449.
. Liu, H.; Cao, X.; Wu, Y.; Liao, Q.; Jimenez, A. J.; W u€ rthner, F.; Fu, H. Chem.
Standard flash chromatography was performed on an IsoleraÔ
Spektra Systems automated with high performance flash purifica-
tion system.
Commun. 2014, 4620e4623.
5. Watson, W. D. J. Org. Chem. 1985, 50, 2145e2148.
6
. Mintz, M. J.; Walling, C. Org. Synth. 1973, 5, 184e185.
4
.2. Synthesis of N-chloramines
7. Rodriguez, R. A.; Pan, C.-M.; Yabe, Y.; Kawamata, Y.; Eastgate, M. D.; Baran, P. S. J.
Am. Chem. Soc. 2014, 136, 6908e6911.
All N-chloramines were synthesized according to a literature
8. Qiu, D.; Mo, F.; Zheng, Z.; Zhang, Y.; Wang, J. Org. Lett. 2010, 12, 5474e5477.
9. Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. Chem.
Lett. 2003, 32, 932e933.
2
5
known procedure described by Bella et al. 1-Chloropiperidine
1a) 1H NMR (300 MHz, CDCl
3.14 (br s, 4H), 1.81e1.63 (m,
H), 1.46 (br s, 2H). 4-Chloromorpholine (1b)
CDCl 3.72 (br s, 2H), 3.14 (br s, 2H). N-Benzyl-N-chloro-1-phe-
nylmethanamine (1c) m H NMR (300 MHz, CDCl
m, 5H), 4.16 (s, 2H). N-Chloro-N-methoxy-benzamide (1d)
NMR (400 MHz, CDCl ): 7.83e7.74 (m, 2H), 7.63e7.52 (m, 1H),
(
4
3
) d
10. Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett. 2006, 8,
2
6 1
H NMR (400 MHz,
2523e2526.
11. Prakash, G. K. S.; Mathew, T.; Hoole, D.; Esteves, P. M.; Wang, Q.; Rasul, G.; Olah,
3
) d
G. A. J. Am. Chem. Soc. 2004, 126, 15770e15776.
2
7
1
3
) d 7.45e7.27
12. Zhang, Y.; Shibatomi, K.; Yamamoto, H. Synlett 2005, 2005, 2837e2842.
2
8 1
(
H
13. Maddox, S. M.; Nalbandian, C. J.; Smith, D. E.; Gustafson, J. L. Org. Lett. 2015, 17,
1
042e1045.
4. Smith, J. R. L.; McKeer, L. C.; Taylor, J. M. J. Chem. Soc., Perkin Trans. 2 1989,
537e1543.
5. Minisci, F.; Vismara, E.; Fontana, F.; Platone, E.; Faraci, G. J. Chem. Soc., Perkin
Trans. 2 1989, 123e126.
6. Koval’, I. V. Russ. J. Org. Chem. 2002, 38, 301e337.
7. Qin, Q.; Ren, D.; Yu, S. Org. Biomol. Chem. 2015, 13, 10295e10298.
8. Qin, Q.; Yu, S. Org. Lett. 2015, 17, 1894e1897.
9. Neumann, M.; F u€ ldner, S.; K o€ nig, B.; Zeitler, K. Angew. Chem., Int. Ed. 2011, 50,
51e954.
0. Romero, N. A.; Nicewicz, D. A. J. Am. Chem. Soc. 2014.
3
d
1
7
.49e7.41 (m, 2H), 3.88 (s, 3H).
1
1
4
.3. General procedure for the photocatalytic activation of N-
chloro compounds
1
1
1
1
In a 5 mL crimp cap vial 0.25 mmol of the respective substrate,
together with 0.3 mmol (1.2 equiv) of the N-chloramine or NCS,
9
2
0
[
.3 mmol (1.2 equiv) (NH
Ru(bpy) ]Cl O were dissolved in 2 mL of MeCN/water 4:1.
ꢂ6H
The reaction mixture was degassed by three cycles of freeze-pump-
thaw and irradiated for 16 h with blue LEDs (
max¼455 nm). For GC
analysis 500 L of the reaction mixture was added to 500 L of the
4
)
S
2 2
O
8
, and 2 mol % (0.005 mmol)
21. Ohkubo, K.; Mizushima, K.; Fukuzumi, S. Res. Chem. Intermed. 2013, 39,
205e220.
3
2
2
22. Shi, L.; Xia, W. Chem. Soc. Rev. 2012, 41, 7687e7697.
23. Teply, F. Collect. Czech. Chem. Commun. 2011, 76, 859e917.
24. Iqbal, N.; Cho, E. J. J. Org. Chem. 2016.
l
m
m
25. Monaco, M. R.; Renzi, P.; Scarpino Schietroma, D. M.; Bella, M. Org. Lett. 2011, 13,
546e4549.
4
standard solution (0.1 M), anisole for dimethoxybenzene, toluene
for anisole, mixed, filtered and submitted to GC analysis. For Tables
2
2
6. Barker, T. J.; Jarvo, E. R. J. Am. Chem. Soc. 2009, 131, 15598e15599.
7. Pandiancherri, S.; Lupton, D. W. Tetrahedron Lett. 2011, 52, 671e674.
4
and 5: After the irradiation the internal standard (0.01 mmol n-
28. Kawase, M.; Kitamura, T.; Kikugawa, Y. J. Org. Chem. 1989, 54, 3394e3403.
Please cite this article in press as: Hering, T.; K o€ nig, B., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.06.028