Visible light driven hydro-/deuterodefunctionalization of anilines

Article abstract of DOI:10.1002/chem.201406461

The defunctionalization of anilines is an important strategy in aromatic-substitution chemistry. Herein, we report on visible light mediated hydro- and deuterodediazonations in solutions of DMF. The mild reaction conditions (DMF, RT, no additives) tolerate various functional groups and allow the site-specific introduction of D atoms to the arene. Mechanistic investigations indicate the participation of photoredox and radical chain pathways and competing abstraction of methyl and formyl hydrogen atoms from DMF.

Full text of DOI:10.1002/chem.201406461

Supporting Information
ꢀ
Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2015
Visible Light Driven Hydro-/Deuterodefunctionalization of
Anilines
[
a]
Michal Majek, Fabiana Filace, and Axel Jacobi von Wangelin*
chem_201406461_sm_miscellaneous_information.pdf

Supporting Information

General methods
Commercial chemicals were used as obtained from Sigma-Aldrich, TCI Europe or
Fisher. Solvents were used without further purification. d
1
-DMF, d
6
-DMF and d -DMF
7
were obtained from Deutero GmbH. TLC was performed on commercial silica gel coated
aluminium plates (DC60 F254, Merck). Visualization was done with UV light or by
staining with phosphomolybdenic acid for UV-inactive compounds. Column
chromatography was performed using silica gel (60 Å pore size, Acros Organics) as the
stationary phase. Product yields were determined by GC-FID (7820A Agilent) using
n-pentadecane as internal standard. The purity and structure of isolated compounds
1
2
13
were confirmed by H NMR, D NMR, C NMR, and MS spectra and comparison with
authentic samples. NMR spectral data were collected on a Bruker Avance 400 (400 MHz
1
13
2
for H; 100 MHz for C) or on a Bruker Avance 600 (92.1 MHz for D) spectrometers at
2
5 °C. Chemical shifts are reported in /ppm, and coupling constants J are given in
Hertz. Solvent residual peaks were used as internal reference for all NMR
measurements. Abbreviations: s – singlet, d – doublet, t – triplet, q – quartet, m –
multiplet, dd – doublet of doublet.

General procedure for the synthesis of arenediazonium tetrafluoroborates:
The aniline (4.5 mmol) was dissolved in glacial acetic acid (3 mL) and 48 % aqueous
tetrafluoroboric acid (1.3 mL). Then, a solution of iso-amylnitrite (1 mL) in glacial acetic
acid (2 mL) was added at room temperature over 5 min. Diethylether (15 mL) was added
and the reaction mixture was cooled down to -30 °C in order to induce crystallization of
the product. The crystals were filtered off in vacuo, washed with diethylether (2 x 10 mL)
and dried on air.
General procedure for the hydrodediazonation:
The arenediazonium tetrafluoroborate (0.25 mmol) and eosin B, disodium salt (3.2 mg,
5
μmol, 2 mol%) were dissolved in DMF (2 mL) in the dark. Nitrogen was bubbled
through the solution during vigorous stirring, and the reaction vessel was capped. The
solution was subjected to irradiation with green light (LEDs, 3.8 W each, λmax 535 nm)
for 30 min at ambient temperature (18 °C). The end point of the reaction was indicated
by the cessation of gas evolution and/or TLC analysis. The reaction mixture was diluted
with diethyl ether (5 mL) and washed with water (5 mL). The aqueous layer was
extracted with diethyl ether (2×5 mL), the organic layers were combined, washed with
brine (5 mL), and dried (Na
separated from the solvent DMF by distillation; non-polar arenes can be separated by
liquid extraction with pentane. The residues were subjected to SiO flash
2
SO
4
). Products with high boiling points can easily be
2
chromatography to isolate the pure benzenes or deuterobenzenes. For screening
purposes, the internal GC standard n-pentadecane (20 μL) was added and the yield was
determined by quantitative GC-FID.

General procedure for the deutero dediazonation:
The arenediazonium tetrafluoroborate (0.25 mmol) and eosin B, disodium salt (3.2 mg,
5
μmol, 2 mol%) were dissolved in d -DMF (0.8 mL) in the dark. Nitrogen was bubbled
7
through the solution during vigorous stirring, and the reaction vessel was capped. The
solution was subjected to irradiation with green light (LEDs, 3.8 W each, λmax 535 nm)
for 7 h at ambient temperature (18 °C). The end point of the reaction was indicated by
the cessation of gas evolution and/or TLC analysis. The reaction mixture was diluted
with diethyl ether (5 mL) and washed with water (5 mL). The aqueous layer was
extracted with diethyl ether (2×5 ml), the organic layers were combined, washed with
brine (5 mL), and dried (Na
2
SO ). The solvent was evaporated in vacuo and the residue
4
purified by column chromatography (silica gel, eluent: pentane) to obtain the pure
deuterated arene.

2
1
1
7
1
,3,5-Trichloro[2- H]benzene: H NMR (400 MHz, CDCl , ppm): 
3
13
.27 (s, 2H); C NMR (100 MHz, CDCl
3
, ppm): 135.6 (C), 135.5 (C),
27.2 (CH), 126.9 (t, 1JCD = 26 Hz, CD); H NMR (92.1 MHz,
2
3 3
CH COCH , ppm): 7.55 (s, 1D); HRMS: calc’d: 180.9363; found: 180.93625.
-Methoxy-3-nitro[4- H]benzene: 1H NMR (400 MHz, CDCl
2
,
1
3
ppm):  7.68 (d, 4JHH = 2.5 Hz, 1H), 7.39 (d, 3JHH = 8.3 Hz, 1H), 7.18
dd, 3JHH = 8.3 Hz, 4JHH = 2.5 Hz, 1H); C NMR (100 MHz, CDCl
13
(
3
, ppm): 160.2 (C),
49.2 (C), 129.9 (CH), 121.4 (CH), 115.6 (t, 1JCD = 26 Hz, CD) 108.1 (CH); H NMR
2
1
(
92.1 MHz, CH
3
COCH , ppm): 7.91 (s, 1D); HRMS: calc’d: 154.0489; found:
3
1
54.04864.
2
1
Methyl [2- H]benzoate: H NMR (400 MHz, CDCl
3
, ppm):  8.04
3
4
3
(
dd, J(H-H) = 8.1 Hz, J(H-H) = 1.2 Hz, 1H), 7.56 (dt, J (H-H) = 7.5
Hz, 3JHH = 1.2 Hz, 1H), 7.45-7.42 (m, 2H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl
,
3
ppm): 167.1 (CO), 132.9 (CH), 130.1 (C), 129.6 (CH), 129.3 (t, 1JCD = 25 Hz, CD),
2
1
28.4 (CH) 128.3 (CH), 52.1 (CH
3
); H NMR (92.1 MHz, CH
3
COCH , ppm): 7.91
3
(s, 1D).
2
1
, ppm):  7.62 (d, 3JHH
[
4- H]Biphenyl: H NMR (400 MHz, CDCl
3
=
8.2 Hz, 4H), 7.49-7.44 (m, 4H), 7.37 (tt, 3JHH = 7.4 Hz, 3JHH
=

13
1
.2 Hz, 1H); C NMR (100 MHz, CDCl
3
, ppm): 141.3 (2 C), 128.8 (2 CH), 128.7 (2
CH), 127.3 (CH), 127.2 (4 CH), 127.0 (t, 1JCD = 25 Hz, CD); H NMR (92.1 MHz,
2
CH
3
COCH , ppm): 7.91 (s, 1D).
3

Calculation of redox potentials:
All reported values are referenced against SCE. The redox potential of eosin B in its
1d
excited state can be obtained from the literature values of the triplet state energy and
from the ground state reduction potential.1c
·
+
E
=
=
red(EB /EB(T
1
))
)) – E(EB(S
-1.97 + 0.60 V = -1.37 V.
·
+
[E(EB(T
1
1
))] – Ered(EB /EB(S ))
1
+
.
Redox potentials of the dmf /dmf couples (DMF-based cations 1A or 1B; radicals 2A or
2
B) were not available but were obtained from DFT calculations (Gaussian G03)2
3
following a well-precedented method for the estimation of SET redox potentials. The
geometries were optimized at the 6-31+G(d,p)/UB3LYP level, single point calculations
with aug-cc-pVTZ/UB3LYP. The solvation was considered in both optimizations as well
as single point calculations using the PCM model with universal force field radii to
approximate the molecule surface. The following values were used to implement DMF
as solvent into the PCM model: permittivity = 36.7; solvent radius = 5.04 Å; density =
0
.00781 molecules per cubic Ångström. Both forms of DMF-based radical and cation
(1A, 1B and 2A, 2B) were taken into consideration.

DFT: E(2A/1A) = 4.44 V; E(2B/1B) = 4.48 V.
These are absolute values referenced to infinity. Reference against SCE requires
abstraction of 4.19 V from these values:3
E
red(2A/1A) = 0.25 V; Ered (2B/1B) = 0.29 V.
Calculation of transition state energies:
2
All DFT calculations were performed using the Gaussian G03 package. Instead of the
standard UB3LYP, the UMPW1K functional was used, which has been shown to perform
better in cases of proton-coupled electron transfer processes.4
Estimation of isotope incorporation:
For determination of H/D isotope incorporation, p-nitrobenzenediazonium
tetrafluoroborate was chosen as model system. The H/D ratio was obtained from
1
integration of H NMR spectra by comparing signal intensities of the product mixture
1
(
nitrobenzene and 4-deuteronitrobenzene at H signals at 8.25 ppm and 7.55 ppm, only
H) with the resonance of the para-CH at 7.71 ppm (H or D). The selectivity of H/D
abstraction from DMF were calculated from this ratio.

References:
1 Redox potentials of arenediazonium salts: a) McCreery, R. L.; Yang, H.-H. Anal.
Chem. 1999, 71, 4081-4087; b) Allongue, P.; Delamar, M.; Desbat, B.;
Fagebaume, O.; Hitmi, R.; Pinson, J.; Saveant, J.-M. J. Am. Chem. Soc. 1997,
1
19, 201-207. Eosin B ground state reduction potential: c) McSkimming, A.;
Colbran, S. B. Chem. Soc. Rev. 2013, 42, 5439-5488. Eosin B tripet energy: d)
DeRosa, M. C.; Crutchley, R. J. Coord. Chem. Rev. 2002, 233-234, 351-371.
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma,
K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.;
Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.;
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez,
C.; Pople, J. A. Gaussian 03, Rev. C.02, Gaussian Inc., Wallingford, 2004.
Baik, M.-H.; Friesner, R. A. J. Phys. Chem. A 2002, 106, 7407-7412.
2
3

4
a) Lingwood, M.; Hammond, J. R.; Hrovat, D. A.; Mayer, J. M.; Borden, W. T. J.
Chem. Theory Comput. 2006, 2, 740-745; b) Jing, L.; Nash, J. J.; Kenttämaa, H.
I. J. Am. Chem. Soc. 2008, 130, 17697-17709.

Selected NMR spectra of products:
1H:
13C:

2H:
1H:

13C:
2H:

1H:
13C:

1H:
13C:

Optimized geometries:
H-abstraction from DMF:
C
O
N
C
H
H
H
C
H
H
H
0.86723100 -0.64973800
2.00055700 -0.20095400
-0.31380900 -0.04721200 -0.00085500
0.00000300
0.00018400
-0.44432400
-0.99481800
-0.98864400
0.54829700
1.41960600
1.74153500 -0.88928300
1.74122600 0.89349100
1.86860200 -0.00323200
0.00023700
0.00012700
-1.55242200 -0.82683300
-2.14566400 -0.58886800 -0.88856500
-1.30816700 -1.88923800 -0.00299600
-2.14170100 -0.59335000
0.89290200
C
O
N
C
H
H
C
H
H
H
H
-0.82474500 -0.63638800 -0.00005300
-1.94267700 -0.10440900 0.00003200
0.06331800 -0.00005500
1.43419500 0.00008000
1.93074200 -0.00051000
0.35629300
0.37775100
1.33637900
-0.56419900
1.96048700
1.63197300 -0.66715700
2.20735600 -0.40990100
0.00010900
0.00005300
0.89270000
1.43463800 -1.73921900 -0.00061900
-0.68470200 -1.72503400 -0.00014900
2.20801000 -0.40893500 -0.89188900
C
O
N
C
-0.94945200 -0.00255000
-2.09844000 -0.00214000 -0.00000100
0.30942100 -0.00038800 -0.00013800
0.00007500
1.06672200
1.29317100
0.00007100

H
H
H
C
H
H
H
1.68645400
1.67260100
0.36668600
1.07347700 -1.28941600
1.67723300 -1.30848300
1.30440300
1.31339200 -0.90527100
2.12578100
0.89615600
0.00932200
0.00001200
0.90686100
0.37840100 -2.12609300 -0.01263900
1.69571500 -1.29639700 -0.89440200
C
O
N
C
H
H
C
H
H
H
H
0.87485100 -0.65919000 -0.00208900
1.93134300 -0.10522800
0.00103800
-0.39525500
-0.34352500
-1.26230400
0.62893300
0.10842800 -0.00103900
1.39218500 -0.00175600
1.96897000
1.87576500
0.00497000
0.00540100
0.00070200
-1.67224900 -0.65204100
-2.23589100 -0.39264200 -0.89443200
-1.44231900 -1.71537000 -0.00401000
0.70254900 -1.74051900
-2.22938500 -0.39910000
0.00419800
0.90169900
Transition states of H-abstraction:
C
C
C
C
C
C
H
H
H
H
H
C
O
N
C
H
H
H
C
0.45118400
1.83174000
2.49117600
1.83130700 -1.21525100 -0.09875500
0.45075200 -1.21130600 -0.23530600
-0.20183500
-0.08862600
2.39755300
2.39679200 -2.13184800 -0.05332600
-0.08939000 -2.14406600 -0.30501000
-1.68913600
-2.90633700
-3.28612700
-3.65598700 -0.00322700
-5.09669000 -0.00277900
-5.50890400 -0.89197600
-5.50933800
-5.37282300
-3.08430000 -0.01366600
1.21526400 -0.21797500
1.21675900 -0.08138700
0.00015300 -0.02235400
0.00252800 -0.28719400
2.14911500 -0.27434300
2.13241200 -0.02287300
0.00408100 -0.46667600
0.00584800 -0.70689100
0.01494900 -1.84742800
0.40264700
0.30276000
0.77859400
0.79241300
0.87868200
0.00533600 -0.74523400
1.72327200

H
H
H
N
O
O
-3.39987500 -0.90227700
-2.00129300 -0.01279200
2.26957700
1.65938700
2.28379000
0.12472200
0.17450600
0.18980900
-3.40045100
0.86584100
3.93986100 -0.00115800
4.49764600 -1.07321900
4.49803200
1.06988100
C
C
C
C
C
C
H
H
H
H
H
C
H
H
N
C
H
H
H
C
H
O
N
O
O
-2.19313700
-0.86337300
0.10028500
-0.19294000 -0.64231400 -0.20294700
-1.52148900 -1.02842400 -0.09610100
-2.49240300 -0.04309500 -0.02971900
-2.99051900
-0.60245000
1.53002500
0.58458600 -1.39043700 -0.25637400
-1.81212600 -2.06597900 -0.06382800
2.73190600
2.91154000
2.87607200
3.49694600
3.51835200
4.14095600 -0.66841000
3.92752700
2.51198400
1.30872900 -0.06553700
1.68937600 -0.17236600
0.70487600 -0.23827800
2.03201000 -0.01034000
2.73707300 -0.20254200
1.09850200 -0.36650700
1.34742400 -0.47850000
1.44592400 -1.54459800
2.29446900
0.30618700
0.18005400
0.03625400
0.09182200
1.52814200
1.78729000
1.97755600
1.91443100
1.08335000
0.02116200
4.08806500 -0.63867300 -0.68177300
3.98363000 -0.42744900 -1.75430700
4.67741300 -1.60786200 -0.26726700
-3.88779800 -0.44506900
-4.72028100 0.43046200
-4.12924100 -1.62957000
0.08288100
0.14015300
0.11242800