Catalyst-free synthesis of phenanthridinesviaelectrochemical coupling of 2-isocyanobiphenyls and amines

Article abstract of DOI:10.1039/d1nj00250c

Catalyst free synthesis of 6-aryl phenanthridines and amides through an electrochemical reaction is reported in this study. The coupling reaction proceeds by the cathodic reduction ofin situformed diazonium ions, which are formed from anilines and an alkyl nitrite. The generated aryl radical diazonium ions coupled from isocyanides furnished the desired products in good yields. This cascade reaction was conducted in an undivided cell equipped with an RVC as the anode and Pt as the cathode usingnBu₄NBF₄as the electrolyte at room temperature. A series of detailed mechanistic studies have also been performed, including a radical clock experiment and cyclic voltammetry analysis.

Full text of DOI:10.1039/d1nj00250c

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Catalyst-free synthesis of phenanthridines via
electrochemical coupling of 2-isocyanobiphenyls
and amines†
Cite this: New J. Chem., 2021,
45, 6367
Bhanwar Kumar Malviya,a Karandeep Singh,a Pradeep K. Jaiswal,b
d
Manvika Karnatak,c Ved Prakash Verma,c Satpal Singh Badsara
and
a
Siddharth Sharma
*
Catalyst free synthesis of 6-aryl phenanthridines and amides through an electrochemical reaction is
reported in this study. The coupling reaction proceeds by the cathodic reduction of in situ formed
diazonium ions, which are formed from anilines and an alkyl nitrite. The generated aryl radical diazonium
ions coupled from isocyanides furnished the desired products in good yields. This cascade reaction was
conducted in an undivided cell equipped with an RVC as the anode and Pt as the cathode using
nBu4NBF4 as the electrolyte at room temperature. A series of detailed mechanistic studies have also
been performed, including a radical clock experiment and cyclic voltammetry analysis.
Received 15th January 2021,
Accepted 19th February 2021
DOI: 10.1039/d1nj00250c
rsc.li/njc
Recently, Mao and Zhou’s group developed a visible light
promoted synthesis of 6-substituted phenanthridines by
Introduction
Phenanthridines are privileged structural motifs due to the sub- the trapping of aryl radicals generated by hydrazine and
stantial interest in the fields of pharmaceuticals and medicinally 2-isocyanobiphenyls.7 Despite these significant advances, the
relevant natural products.1 The 6-aryl phenanthridine nucleus intrinsic shortcomings associated with transition metals/
based structural motifs (such as ethidium bromide) were oxidants, harsh reaction conditions and the low substrate scope
associated with a unique property related to the intercalation (phenyl hydrazines as the coupling partner) are some significant
with DNA and RNA and/or a fluorescent marker for ds-DNA and issues and reasons for developing the improved methods.
ds-RNA (Fig. 1).2
Over the years, prosperous development of sustainable and
Consequently, the development of novel strategies for environment friendly processes for chemical transformation
synthesizing phenanthridines is highly desirable.3,4 Conventionally, has led to remarkable progress and organic electrochemistry
the Bischler–Napieralski reaction has been used for the pre- has efficiently contributed in this direction.8 Organic electro-
paration of phenanthridine derivatives in the presence of POCl3 chemistry is a broad term that defines chemical synthesis
or PCl5 at elevated temperatures. In a pioneering work, Chatani where activation is induced by electrons commonly consisting
and co-workers demonstrated phenyl radical insertion, of anodic oxidations and cathodic reductions, replacing costly
generated by phenyl boronic acid using a Mn(III) catalyst, into and toxic metal catalysts. Nonetheless, precise and regulated
2-isocyanobiphenyls for the phenanthridine synthesis.5 generation of reactive radicals to achieve predictable and tunable
In 2014, Zhu’s group synthesized phenanthridine derivatives chemo-selectivity is still an enormous challenge. Recently,
by arylative cyclization of 2-isocyanobiphenyls using oxidative Studer and co-workers demonstrated a very important trifluoro-
insertion of anilines as the arylating source (Scheme 1a).6 methyl radical insertion, generated by the Togni reagent, into
2-isocyanobiphenyls for the phenanthridine synthesis
(Scheme 1b).9 This electrochemical synthesis requires no
catalysts or oxidizing agents and provides efficient and scalable
a Department of Chemistry, Mohanlal Sukhadia University, Udaipur, 313001, India.
E-mail: siddharth@mlsu.ac.in, sidcdri@gmail.com
b Department of Biochemistry and Biophysics, Texas A&M University,
access to a range of phenanthridine and alike molecules.10
Nevertheless, electrochemical aryl radical generation directly by
amine via the reduction of in situ generated diazonium salts is
relatively mild in nature but scarce in the literature.11–16
Inspired by the above works, and from our recent experience
in isocyanide chemistry,17 here we have utilized isocyanides for
electrochemical oxidative cross-coupling with amines for
College station, Texas, 77843, USA
c Department of Chemistry, Banasthali University, Newai-Jodhpuriya Road,
Vanasthali, 304022, India
d Department of Chemistry, University of Rajasthan, Jaipur, 302004, India
† Electronic supplementary information (ESI) available: Copy of 1H NMR and 13
C
NMR of all the synthesized compounds and CV studies. See DOI: 10.1039/
d1nj00250c
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Fig. 1 Some representative alkaloids and bioactive phenanthridines.
carbodiimide synthesis.18 We surmised whether the produced inferior results compared with acetonitrile (Table 1,
electrochemically generated aryl radicals could be trapped by entries 6–8). Due to the potential effect of electrode materials to
isocyanides. Herein, we report the first electrochemical synthesis achieve the desired product 3a in excellent yield, the RVC as the
of 6-aryl phenanthridines and amides under mild conditions anode and Pt as the cathode were established as the best
without the involvement of catalysts, metals and oxidants.
electrode for this electrolysis reaction, although comparable
results were obtained when Pt was used as the anode in place of
RVC (Table 1, entry 9). Other metal electrodes such as Cu and
Ni were relatively less effective when used as cathodes (Table 1,
entries 10–11). Extending the reaction time does not affect the
Results and discussion
Building upon previous works, our early efforts demonstrated reaction yield much but reducing the reaction time to 6 h
that electrochemically generated phenyl radicals from in situ reduced the yield of 3a drastically (Table 1, entries 12 and 13).
generated phenyl diazonium salt from aniline 1a could be
Similarly, conducting the electrolysis using higher density
trapped by biphenylisocyanide 2a for the synthesis of (20 mA) also considerably reduced the yield of 3a (Table 1, entry
6-arylated phenanthridine 3a (Table 1). The electrochemical 14) and biphenyl 6 was the major product isolated (yield 49%).
intramolecular cyclization cascade reaction was conducted at a Moreover, when the reaction was performed under an air
constant current in an undivided cell equipped with an oxidatively atmosphere, a decrease in the product yield was observed
robust reticulated vitreous carbon (RVC) as the anode (working (Table 1, entry 18). Among the nitrite sources used such as
electrode), and platinum (Pt), as the cathode (counter electrode). t-BuONO and n-BuONO, isoamyl nitrite (i-AmONO) was the best
After screening a wide range of reaction systems, the desired (entries 19 and 20).
6-arylated phenanthridines 3a were prepared in 81% yield using
With the optimized conditions in hand, we next studied the
CH3CN/HFIP (10 : 1) as solvent and nBu4NBF4 (0.1 M) as substrate scope and generality of the present methodology for
electrolyte under a constant current of 5 mA for 16 h (Table 1, the synthesis of phenanthridines 3a–w by varying the aryl
entry 2). However, to our surprise, 84% yield of 3a was obtained amines 1 and 2-isocyanobiphenyls 2 (Table 2). A variety of
when 10 mA current was applied in 0.05 M electrolyte for 16 h different functional groups at aryl amines 1, that bear both
(Table 1, entry 1). It is important to note that we could reduce the electron-donating groups (CH3, OCH3) and electron-
costly electrolyte amount to half just by changing the applied withdrawing groups (F, Cl, Br, CN), showed great compatibility
current.
to give the corresponding products 3a–u in moderate to
Among the series of supporting electrolytes that were excellent yields (Table 2). Different aryl amine bearing
screened, no product 3a was detected when nBu4NBF4 was electron-donating CH3 and OCH3 at the para-position provided
replaced with NH4I whereas in the presence of LiClO4 and the corresponding products 3b, 3c, 3h, and 3n in 54–72%
nBu4NPF6 it was isolated in lower yields (Table 1, entries 1 and yields, whereas the electron-withdrawing groups on aryl amines
3–5). HFIP was found to be the best co-solvent with CH3CN, 3d–f, 3i–l, and 3p–q furnished good isolated yields of up to
possibly due to its low nucleophilic and protic nature, which 81%, possibly due to alteration in radical activity due to the
could enhance the stability of radical or cationic intermediates. presence of an electron withdrawing group. It is to be noted
The use of other solvents, such as THF, MeOH and DMF that the unsubstituted aryl amines and 2-isocyanobiphenyl
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Scheme 1 Some previous reports showing conventional pathways towards utilizing C-centred radical trapping.
furnished phenanthridine 3a in excellent yield (Table 2, entry 1, (3s–t) in moderate yields of up to 62% yield. However, chloro
84%). The reaction was very amenable, when different substituted biphenyl isocyanide and heteroaromatic amine did
substituted 2-isocyanobiphenyls were used (3f–3q), whereas, not couple under standard conditions (3v, 3w, 3x).
few phenanthridine fused heteroaromatic polycyclic compounds
At this juncture, we inquired whether this mode of phenyl
were also well amenable to the standard reaction conditions radical generation could be extended to other related
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Table 1 Optimization studya
Next, we evaluated the scalability of this isocyanide insertion
by performing reactions on a 5 mmol scale. The reaction with
amine 1a with biphenylisocyanide 2a smoothly furnished the
desired product 3a (1.00 g) in 79% yield (Scheme 2). This result
shows the potential of this insertion reaction in practical
synthesis.
To gain insight into the mechanism of this method, we
Yieldb [%] conducted control experiments, as shown in Scheme 3, to
Entry Variation from standard conditionsa
explore the existence of putative radical intermediates. In a
1
None
84
control experiment, in the absence of isocyanides, biphenyl 6
was observed as the sole product during electrolysis (Scheme 3,
eqn (a)). Thus, radical intermediates are possibly involved
2
3
4
5
5 mA instead of 10 mA, 16 h and nBu4NBF4 (0.1 M) 81
NH4I instead of nBu4NBF4
0
LiClO4 instead of nBu4NBF4
nBu4NPF6 instead of nBu4NBF4
67
63
under the electrolysis conditions. We have also investigated the
reaction mechanism under our optimized reaction conditions
with a radical clock substrate, 2-(allyoxy)phenylamine 7. This
radical clock experiment gave the bicyclic phenanthridine 8
detected by HRMS (Scheme 3, eqn (b)), which again confirmed
unambiguously to a radical mechanism. Similarly, the reaction of
benzenediazonium tetrafluoroborate 9 under standard reaction
conditions gave the corresponding product 3a in good yields,
again indicating the possible radical mechanism followed in the
reaction.
Furthermore, we also carried out cyclic voltammetry (CV)
experiments to study the redox potential of the substrates
(Fig. 2). Two reduction peaks were observed at ꢀ0.34 V and
ꢀ1.92 V in nBu4NBF4 (0.05 M) as an electrolyte in CH3CN, two
reduction peaks, corresponding to the in situ reduction of aryl
diazonium to aryl radicals and possibly further to aryl anion,
respectively (for detailed analysis of CV please see the ESI† and
Fig. S1–S5). On the basis of the control experimental results and
6
7
8
9
THF instead of CH3CN
MeOH instead of HFIP
DMF instead of CH3CN
Pt (+)/Pt (ꢀ) instead of RVC (+)/Pt (ꢀ)
RVC (+)/Cu (ꢀ) instead of RVC (+)/Pt (ꢀ)
RVC (+)/Ni (ꢀ) instead of RVC (+)/Pt (ꢀ)
24 h instead of 16 h
10 h instead of 16 h
20 mA instead of 10 mA
No electric current
50 1C instead of RT
5 mA instead of 10 mA and nBu4NBF4 (0.05 M)
Under air
t-BuONO instead of i-AmONO
n-BuONO instead of i-AmONO
No electric current and 80 1C
27
22
47
77
56
67
80
36
32
0
16
49
13
62
51
0
10
11
12
13
14
15
16
17
18
19
20
21
a
Reaction conditions: all reactions were performed with an RVC anode,
Pt cathode, constant current = 10 mA, 1a (1.5 mmol), 2a (0.50 mmol),
i-AmONO (1.5 equiv.), nBu4NBF4 (0.05 M), CH3CN/HFIP (10 : 1),
(1F molꢀ1), 25 1C, 16 h. The yield of 3a was isolated.
b
transformations by isocyanide trapping. Therefore, the electro- literature reports13 a plausible mechanism for the electro-
chemical oxidative cyclization was further extended to similar chemical oxidative cyclization reaction is proposed, as shown
optimization reaction condition for the synthesis of amides in Scheme 4. Initially, aryldiazonium ion A was formed from
5a–n. After a series of screening of reaction conditions, we anilines and i-AmONO. Then, the aryl radical B was generated
found that the direct electrolysis of aryl amines in an electrolyte by single-electron-transfer (SET) reduction of the aryl diazo-
solution of nBu4NBF4 in CH3CN/H2O (10 : 1) furnished amides nium salt A on the cathode. Phenanthridine synthesis was
in good to excellent yields. As shown in Table 3, a variety of aryl achieved by the formation of intermediate C by the coupling
amines having both electron-donating groups (CH3, OCH3) and of B and 2. Intramolecular cyclization of C and subsequent
electron-withdrawing groups (NO2, Br, F) were tested with oxidative aromatization at the anode led to the corresponding
t-butyl isocyanides and smoothly furnished the desired amides carbocation E. Finally, removal of a proton from E afforded the
5a–g in good yields (Table 3). Different isocyanides were also targeted heterocycle 3. Similarly, the generated aryl radical
examined under our optimized reaction conditions and intermediate undergoes direct coupling with the isocyanide 4
furnished the desired products 5h–m in moderate to good to afford an imidoyl intermediate G. Finally, the hydration of
yields. Electron-withdrawing groups present on the benzene imidoyl cation G leads to the formation of the amides 5.
ring of phenyl amines such as NO2 and Br led to very good
yields (up to 81%) of amides 5e–g (Table 3). By using different
aliphatic isocyanides with substituents like cyclohexyl, benzyl
and indolylethyl, a series of amides 5h–n were successfully
Conclusions
synthesized. Notably, the aromatic isocyanides containing an In summary, we have devised
a highly atom-economical
electron-donating group at the para position exhibited good synthesis of 6-aryl substituted phenanthridines 3 by means of a
reactivity, as product 5j was obtained in 84% yield. In addition, radical-triggered pathway that involves a phenyl radical generated
2,6-dimethyl substituted phenylisocyanide performed with from aryl amines and 2-arylisocynides. Moreover, the electro-
lesser reactivity and furnished the amide 5k in 54% yield chemical technology is also suitable for amides 5 using a similar
whereas 4-bromophenyl isocyanide was well tolerated (5l, 78%). strategy. Under undivided electrolytic conditions, a series of
In addition, one heteroaromatic containing amine was also phenanthridines 3 and amides 5 can be obtained in good to
utilized for the synthesis of amide 5n in moderate yield.
excellent yields. Significantly, this reaction can be conducted on
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Table 2 Substrate scope for the synthesis of phenanthridinesa
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Table 2 (continued)
a
Isolated yields.
Table 3 Substrate scope of the electrochemical synthesis of amidesa
a
Isolated yields.
a gram scale under atmospheric conditions. Furthermore, the
control experiments, to prove the reaction mechanism, and
cyclic voltammetry (CV) experiments, to study the redox potential
of the substrates, were well studied. Further application of
electrochemical isocyanide cross-coupling for other challenging
phenanthridine nuclei is currently underway in our laboratory.
Experimental section
General information
All reactions involving moisture sensitive reagents or inter-
mediates were carried out in pre-heated glassware under a
nitrogen atmosphere. All solvents and chemicals were used as
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Chemical shifts (d) were reported in ppm referenced to an
internal TMS standard for 1H NMR. Chemical shifts of 13C
NMR are reported relative to CDCl3 (d 77.03) and relative to
the signal of DMSO-d6 (d 2.50 ppm for 1H NMR and d 39.52 ppm
for 13C NMR). The following abbreviations were used to describe
peak splitting patterns when appropriate: br s = broad singlet,
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet.
Coupling constants, J, were reported in Hertz (Hz). Mass spectra
were recorded on a Bruker MicroTOF Q II mass spectrometer.
The instrument used for electrolysis was IKA ElectraSyn 2.0 pro
constant current DC power supply with three electrode cyclic
voltammetry attachments and on our inhouse design electrolysis
experiments. An oil bath was used for the heating conditions.
Scheme 2 Gram-scale synthesis.
Representative procedure for the preparation of biphenyl
isocyanides (2)19
All biphenyl isocyanides were prepared according to the
reported method. A typical procedure for the synthesis of 2 is
shown below.
Synthesis of [1,10-biphenyl]-2-amine
To an oven-dried three necked flask, 2-bromoaniline (860 mg,
5 mmol), phenylboronic acid (725 mg, 6 mmol), an aqueous
solution of K2CO3 (2 M, 5 mL) and DMF (10 mL) were added
under a stream of N2. The mixture was stirred for 30 min at
room temperature under an N2 atmosphere. To the stirred
mixture, PdCl2(PPh3)2 (70 mg, 0.10 mmol) was added at room
temperature, and the mixture was stirred overnight at 80 1C.
The reaction mixture was then cooled to room temperature and
diluted with EtOAc. The organic layer was washed with water
and dried over Na2SO4. After removing the volatiles in vacuo, the
residue was subjected to column chromatography on silica gel
(petroleum ether/EtOAc) to afford 2-phenylaniline (750 mg, 82%).
Scheme 3 Control experiments.
Synthesis of N-([1,10-biphenyl]-2-yl)formamide
Acetic formic anhydride (0.89 mL) was added dropwise to a
solution of [1,10-biphenyl]-2-amine (727 mg, 4.30 mmol) at 0 1C
in THF (10 mL) under stirring. The mixture was stirred for 2 h
at room temperature. Then, the mixture was quenched with a
saturated aqueous solution of NaHCO3 (20 mL) and extracted
with EtOAc (30 mL) three times. The extract was dried over
Na2SO4 and concentrated under reduced pressure to give
formamide (717 mg, 3.63 mmol) as a pale yellow oil. This
material was used for the subsequent dehydration without
further purification.
Fig. 2 Cyclic voltammograms of 1a in CH3CN, using a glassy carbon
electrode as the working electrode, a Pt wire as the counter electrode, and
Ag/AgCl as the reference electrode, at a scan rate of 0.1 V sꢀ1: 1a (0.01 M) +
i-AmONO (0.01 M) + nBu4NBF4 (0.05 M).
Synthesis of 2-isocyano-1,10-biphenyl
THF (8 mL), and NEt3 (4.3 mL) were added to the flask containing
N-([1,10-biphenyl]-2-yl)formamide, and POCl3 (0.5 mL, 1.5 eq.) in
2 mL of THF was added slowly via syringe for a period of 1 h at
received from the suppliers (Alfa, Sigma Aldrich, Avra). Reactions 0 1C, and the mixture was stirred for another 2 h at 0 1C. To the
were monitored using thin-layer chromatography (TLC) on reaction mixture was added 15 mL of EtOAc at 0 1C. The mixture
commercial silica gel plates. Solvents for crystallization and was slowly quenched with saturated aqueous solution of NaHCO3
extractions have been distilled once. Column chromatography (20 mL) and stirred for 30 min at 0 1C. Then, the mixture was
1
was performed on silica gel (100–200 mesh). H and 13C NMR extracted with EtOAc (30) three times, dried over Na2SO4 and
spectra were recorded on a 400 MHz and 500 MHz spectrometer. evaporated under reduced pressure. The compound was purified
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Scheme 4 Plausible mechanism.
by column chromatography (petroleum ether/EtOAc 19 : 1, 5%) to finished, the solution was extracted with ethyl acetate (80 mL).
give 2 as a pale yellow solid (650 mg, 3.63 mmol).
The combined organic layer was dried with Na2SO4, filtered. The
solvent was removed with a rotary evaporator. The pure product
was obtained by column chromatography on silica gel (ethyl
General procedure for the synthesis of 3
An undivided cell was equipped with a RVC plate (15 mm ꢁ acetate/petroleum ether 1 : 9 = 10%) yield (1.00 g, 79%).
15 mm ꢁ 5 mm) anode and a platinum plate (15 mm ꢁ 15 mm ꢁ
Characterization of the products
0.3 mm) cathode. The compound aromatic amines 1 (1.5 mmol),
i-AmONO (1.5 equiv.), biphenylisocynide 2 (0.5 mmol) and
supporting electrolyte nBu4NBF4 (0.05 M) in CH3CN/HFIP
6-Phenylphenanthridine (3a)19a,b. White solid, isolated yield
(107 mg, 84%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d
(10 : 1, 6 mL) was first stirred for 10 min, and after the complete 7.53–7.59 (m, 3H), 7.60 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.68 (td,
consumption of amine on TLC, the reaction was electrolyzed J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.73–7.79 (m, 3H), 7.85 (td, J1 = 8 Hz,
under constant current conditions (10 mA at 25 1C) under J2 = 1.2 Hz, 1H), 8.10 (dd, J1 = 8 Hz, J2 = 0.4 Hz, 1H), 8.24 (td, J1 =
nitrogen atmosphere for 16 h. Electrodes were washed with ethyl 8 Hz, J2 = 1.2 Hz, 1H), 8.62 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 8.70
acetate (10 mL), and when the reaction was finished, the (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 122.9, 122.2,
solution was extracted with ethyl acetate (40 mL). The combined 123.7, 125.2, 126.9, 127.1, 128.4, 128.7, 128.8, 128.9, 129.7,
organic layer was dried with Na2SO4, filtered. The solvent was 130.3, 130.6, 133.4, 139.8, 143.8, 161.3.
6-(m-Tolyl)phenanthridine (3b)20a. Brown solid, isolated
removed with a rotary evaporator. The pure product was
obtained by column chromatography on silica gel (ethyl yield (97 mg, 72%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3):
acetate/petroleum ether 1 : 9 = 10%).
d 2.48 (s, 3H), 7.35 (d, J = 7.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H),
7.51 (d, J = 7.6 Hz, 1H), 7.58 (s, 1H), 7.62 (td, J1 = 7.6 Hz, J2 =
0.8 Hz, 1H), 7.69 (td, J1 = 6.8 Hz, J2 = 1.2 Hz, 1H), 7.76 (td, J1 =
Larger-scale synthesis of 3a
An undivided cell (50 mL) was equipped with RVC electrodes 8.4 Hz, J2 = 1.6 Hz, 1H), 7.87 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H),
(20 ꢁ 35 ꢁ 5 mm) as the anode, platinum electrodes (20 ꢁ 35 ꢁ 8.12 (d, J = 8 Hz, 1H), 8.37 (d, J = 7.6 Hz, 1H), 8.62 (d, J = 8.4 Hz,
0.5 mm) as the cathode. Using a stir bar, aniline 1a (1.395 g, 1H), 8.70 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 21.5,
15 mmol), i-AmONO (1.757 g, 15 mmol), 2-isocyano-1,10- 121.9, 122.2, 123.8, 125.1, 126.9, 127.2, 127.3, 128.2, 129.1,
biphenyl 2a (0.896 g, 5.0 mmol), CH3CN/HFIP (10 : 1, 20 mL) 129.3, 129.7, 129.8, 130.4, 131.1, 133.6, 138.3, 161.4.
and supporting electrolyte nBu4NBF4 (0.329 g, 0.05 M) were first
6-(4-Methoxyphenyl)phenanthridine (3c)20a
. White solid,
stirred for 10 min, after the complete consumption of amine on isolated yield (80 mg, 56%) (for 0.5 mmol),1H NMR
TLC reaction was electrolyzed under constant current conditions (400 MHz, CDCl3): d 3.92 (s, 3H), 7.08 (tt, J1 = 8.8 Hz, J2 = 2,
(25 mA at 25 1C) under nitrogen conditions for 40 h. Electrodes 2H), 7.60 (td, J1 = 7.6 Hz, J2 = 0.8, 1H), 7.65 (td, J1 = 7.2 Hz, J2 =
were washed with ethyl acetate (10 mL), when the reaction was 1.2, 1H), 7.70 (dd, J1 = 8.4 Hz, J2 = 2, 2H), 7.73 (td, J1 = 8 Hz, J2 =
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1.2, 1H), 7.83 (td, J1 = 8 Hz, J2 = 0.8, 1H), 8.16 (d, J = 8.4 Hz, 1H), d 22.0, 115.3, 115.5, 121.6, 122.3, 123.6, 125.2, 127.1, 128.6, 129.9,
8.23 (dd, J1 = 8.4 Hz, J2 = 0.8, 1H), 8.60 (d, J = 7.6 Hz, 1H), 8.69 130.5, 130.7, 131.6, 131.7, 133.3, 135.7, 137.1, 141.8, 159.2,
(d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 55.5, 113.9, 161.9, 164.4.
121.9, 122.2, 123.6, 125.4, 126.7, 127.1, 128.8, 128.9, 130.2,
130.5, 131.2, 132.3, 133.5, 143.7, 160.1, 160.9.
6-(3-Chlorophenyl)-2-methylphenanthridine (3j)20b. Brown
solid, isolated yield (100 mg, 66%) (for 0.5 mmol),1H NMR
6-(3-Chlorophenyl)phenanthridine (3d)20a. Brown solid, iso- (400 MHz, CDCl3): d 2.66 (s, 3H), 7.46–7.52 (m, 2H), 7.59–7.64
lated yield (118 mg, 82%) (for 0.5 mmol),1H NMR (400 MHz, (m, 3H), 7.75 (s, 1H), 7.83 (t, J = 7.2 Hz, 1H), 8.03 (d, J = 8 Hz,
CDCl3): d 7.48–7.54 (m, 2H), 7.61–7.66 (m, 2H), 7.69 (td, J1 = 8 Hz, 1H), 8.11 (d, J = 8 Hz, 1H), 8.40 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H);
J2 = 1.2 Hz, 1H), 7.75 (t, J = 2 Hz, 1H), 7.76 (td, J1 = 7.2 Hz, J2 = 13C NMR (100 MHz, CDCl3): d 22.0, 121.6, 122.3, 123.6, 125.0,
1.2 Hz, 1H), 7.86 (td, J1 = 7.6 Hz, J2 = 1.2, 1H), 8.05 (dd, J1 = 8 Hz, 127.2, 128.0, 128.4, 128.8, 129.7, 129.9, 130.1, 130.5, 130.7,
J2 = 0.4 Hz, 1H), 8.25 (dd, J1 = 8 Hz, J2 = 0.8 Hz, 1H), 8.61 (dd, J1 = 133.2, 134.5, 137.2, 141.6, 142.0, 158.7.
8 Hz, J2 = 1.2, 1H), 8.69 (d, J = 8.4, 1H);13C NMR (100 MHz,
6-(4-Bromophenyl)-2,8-dimethylphenanthridine (3k). Light
CDCl3): d 121.9, 122.3, 123.8, 124.9, 127.3, 127.4, 127.9, 128.5, yellow solid, isolated yield (136 mg, 75%) (for 0.5 mmol),1H NMR
128.9, 129.0, 129.7, 129.8, 130.2, 130.9, 133.5, 134.5, 141.2, (400 MHz, CDCl3 + DMSO): d 2.51 (s, 3H), 2.64 (s, 3H), 7.55 (d, J =
143.4, 159.6.
8.4 Hz, 1H), 7.60 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 8 Hz, 3H), 7.79 (s,
6-(4-Bromophenyl)phenanthridine (3e)20a. White solid, isolated 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.36 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H); 13
C
yield (117 mg, 70%) (for 0.5 mmol), 1H NMR (400 MHz, CDCl3): d NMR (100 MHz, CDCl3 + DMSO): d 21.4, 21.7, 121.2, 122.0, 122.8,
7.61–7.65 (m, 3H), 7.68–7.72 (m, 3H), 7.75 (td, J1 = 7.6 Hz, J2 = 1.6, 123.4, 124.5, 127.5, 128.9, 130.1, 130.8, 131.2, 131.2, 132.4, 137.0,
1H), 7.85 (td, J1 = 7.2 Hz, J2 = 1.2, 1H), 8.05 (dd, J1 = 8 Hz, J2 = 0.8, 137.1, 158.1; HRMS (ESI-TOF) m/z [M + H]+calcd for C21H17BrN
1H), 8.22 (dd, J1 = 8 Hz, J2 = 0.8, 1H), 8.61 (dd, J1 = 8 Hz, J2 = 1.6, 362.0539; found 362.0534.
1H), 8.70 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 122.0,
122.3, 123.1, 123.7, 124.9, 127.1, 127.5, 128.4, 128.9, 130.3, 130.7, solid, isolated yield (130 mg, 86%) (for 0.5 mmol), 1H NMR
131.4, 131.6, 133.5, 138.6, 143.7, 159.9. (400 MHz, DMSO-d6): d 2.50 (s, 3H), 2.63 (s, 3H), 7.51 (t, J =
6-(4-Fluorophenyl)-2,8-dimethylphenanthridine (3l). White
6-(4-Bromophenyl)-2-methylphenanthridine (3f)20b. Brown 8.8 Hz, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.82 (s, 1H), 7.87–7.91 (m,
solid, isolated yield (118 mg, 68%) (for 0.5 mmol),1H NMR 2H), 7.99 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.75 (s, 1H),
(400 MHz, CDCl3): d 2.65 (s, 3H), 7.59–7.65 (m, 4H), 7.69 (s, 1H), 8.92 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d 21.2,
7.71 (s, 1H), 7.86 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 8.04 (dd, J1 = 21.6, 115.7, 115.9, 122.6, 123.3, 124.1, 124.4, 129.0, 130.0, 131.8,
8.4 Hz, J2 = 0.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.68 131.9, 132.9, 133.8, 136.1, 139.2, 157.7, 162.3, 164.7; HRMS
(d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 22.1, 121.6, (ESI-TOF) m/z [M + H]+calcd for C21H17FN 302.1340; found
122.4, 123.7, 124.7, 127.4, 128.8, 129.1, 129.5, 131.1, 131.2, 302.1332.
131.6, 131.7, 133.5, 137.6, 158.7.
2,8-Dimethyl-6-phenylphenanthridine (3m)20d. Pale yellow
2-Methyl-6-phenylphenanthridine (3g)20b. Pale yellow solid, solid, isolated yield (80 mg, 57%) (for 0.5 mmol),1H NMR
isolated yield (113 mg, 84%) (for 0.5 mmol),1H NMR (400 MHz, (400 MHz, CDCl3): d 2.48 (s, 3H), 2.62 (s, 3H), 7.51–7.57 (m,
CDCl3): d 2.62 (s, 3H), 7.52 (d, J = 10.8 Hz, 5H), 7.71 (d, J = 6 Hz, 4H), 7.63 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.2 Hz, 2H), 7.83 (s, 1H),
2H), 7.76 (t, J = 8.4 Hz, 1H), 8.05 (d, J = 8 Hz, 1H), 8.12 (d, J = 8 8.14 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 8.53 (d, J = 8.4 Hz, 1H); 13
C
Hz, 1H), 8.35 (s, 1H), 8.62 (d, J = 7.6 Hz, 1H); 13C NMR (100 NMR (100 MHz, CDCl3): d 21.7, 22.0, 121.3, 122.1, 123.6, 125.3,
MHz, CDCl3): d 21.9, 121.5, 122.1, 123.5, 125.2, 126.9, 128.3, 128.2, 128.4, 128.6, 129.7, 129.7, 130.2, 131.1, 132.3, 136.8,
128.5, 128.7, 129.7, 129.9, 130.3, 130.5, 133.1, 136.7, 139.8, 137.0, 139.6, 141.4, 159.9.
141.9, 160.2.
6-(4-Methoxyphenyl)-2,8-dimethylphenanthridine (3n). Pale
6-(4-Methoxyphenyl)-2-methylphenanthridine (3h)19b. White yellow solid, isolated yield (84 mg, 54%) (for 0.5 mmol),1H NMR
solid, isolated yield (99 mg, 66%) (for 0.5 mmol), 1H NMR (400 MHz, CDCl3): d 2.44 (s, 3H), 2.57 (s, 3H), 3.87 (s, 3H), 7.13
(400 MHz, CDCl3): d 2.65 (s, 3H), 3.91 (s, 3H), 7.07 (dt, J1
=
(d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 8.4 Hz,
8.8 Hz, J2 = 2 Hz, 2H), 7.56 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 7.58 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.82 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H),
(td, J1 = 8 Hz, J2 = 1.2 Hz, 1H), 7.68 (dt, J1 = 8.8 Hz, J2 = 2 Hz, 2H), 8.54 (s, 1H), 8.73 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
7.81 (td, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 8.10 (d, J = 8.4 Hz, 2H), 8.13 d 21.7, 21.9, 55.8, 114.2, 122.4, 123.2, 123.6, 124.9, 128.2, 128.4,
(dd, J1 = 8.4 Hz, J2 = 0.8 Hz, 1H), 8.39 (s, 1H), 8.67 (d, J = 8 Hz, 130.9, 131.3, 131.8, 133.6, 137.5, 137.9, 159.0, 160.4; HRMS
1H); 13C NMR (100 MHz, CDCl3): d 22.0, 55.4, 113.9, 121.5, (ESI-TOF) m/z [M + H]+calcd for C22H20NO 314.1539; found
122.2, 123.4, 125.4, 126.9, 128.7, 130.0, 130.2, 130.5, 131.2, 314.1542.
132.4, 133.2, 136.6, 142.2, 159.9, 160.0.
8-Methyl-6-phenylphenanthridine (3o)20e. White solid, iso-
6-(4-Fluorophenyl)-2-methylphenanthridine (3i)20c
.
Pale lated yield (91 mg, 68%) (for 0.5 mmol),1H NMR (400 MHz,
yellow solid, isolated yield (109 mg, 76%) (for 0.5 mmol),1H NMR CDCl3): d 2.48 (s, 3H), 7.52–7.59 (m, 3H), 7.63 (td, J1 = 7.6 Hz,
(400 MHz, CDCl3 + DMSO): d 2.68 (s, 3H), 7.25 (tt, J1 = 8.8 Hz, J2 = J2 = 1.2 Hz, 2H), 7.70 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 3H), 7.85
2.8 Hz, 2H), 7.60 (dd, J1 = 8 Hz, J2 = 2 Hz, 1H), 7.62 (td, J1 = 8 Hz, J2 = (s, 1H), 8.26 (d, J = 8 Hz, 1H), 8.54 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz,
1.2 Hz, 1H), 7.73–7.78 (m, 2H), 7.86 (td, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 2H); 13C NMR (100 MHz, CDCl3): d 21.7, 121.7, 122.1, 123.8,
8.07 (dd, J1 = 8.4 Hz, J2 = 0.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.42 125.3, 126.9, 128.3, 128.4, 128.7, 129.7, 130.0, 131.3, 132.5,
(s, 1H), 8.71 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3 + DMSO): 137.2, 139.5, 143.1, 160.9.
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6-(4-Fluorophenyl)-8-methylphenanthridine (3p). Pale yellow (15 mm ꢁ 15 mm ꢁ 0.3 mm) cathode. The compound of amine
solid, isolated yield (112 mg, 78%) (for 0.5 mmol),1H NMR 1 (1.5 mmol), i-AmONO (1.5 equiv.), isocyanide 4 (0.5 mmol)
(400 MHz, CDCl3 + DMSO): d 2.55 (s, 3H), 7.31 (t, J = 7.2 Hz, 2H), and supporting electrolyte nBu4NBF4 (0.05 M) in CH3CN : H2O
7.74–7.83 (m, 5H), 7.88 (s, 1H), 8.47 (s, 1H), 8.63–8.68 (m, 2H); (10 : 1, 7 mL) was first stirred for 10 min, after the complete
13C NMR (100 MHz, CDCl3 + DMSO): d 20.9, 114.8, 115.0, 121.4, consumption of amine in the TLC reaction it was electrolyzed
121.8, 123.2, 123.7, 126.8, 127.3, 127.8, 128.5, 131.2, 131.3, under constant current conditions (10 mA at 25 1C) under
131.4, 133.7, 137.6, 139.2, 158.4, 161.5, 164.0; HRMS nitrogen conditions for 16 h. Electrodes were washed with ethyl
(ESI-TOF) m/z [M + H]+calcd for C20H15FN 288.1183; found 288.1188. acetate (10 mL), when the reaction was finished, the solution
6-(3-Chlorophenyl)-8-methylphenanthridine (3q). Pale yellow was extracted with ethyl acetate (40 mL). The combined organic
solid, isolated yield (103 mg, 68%) (for 0.5 mmol),1H NMR layer was dried with MgSO4, filtered. The solvent was removed
(400 MHz, CDCl3): d 2.52 (s, 3H), 7.52 (s, 2H), 7.60 (d, J = 4.8 with a rotary evaporator. The pure product was obtained by
Hz, 1H), 7.67–7.76 (m, 4H), 7.80 (s, 1H), 8.28 (d, J = 7.6 Hz, 1H), column chromatography on silica gel (ethyl acetate/petroleum
8.56 (t, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 21.8, 121.8, ether 1 : 4 = 20%).
122.3, 123.9, 125.0, 127.4, 127.9, 128.0, 128.7, 129.0, 129.7, 129.8,
131.5, 132.9, 134.5, 137.6, 159.3; HRMS (ESI-TOF) m/z [M + H]+calcd lated yield (84 mg, 81%) (for 0.5 mmol),1H NMR (400 MHz,
N-(tert-Butyl)-4-methoxybenzamide (5a)21a. White solid, iso-
for C20H15ClN 304.0888; found 304.0888.
CDCl3): d 1.47 (s, 9H), 3.84 (s, 3H), 5.91 (s, 1H), 6.89 (d, J =
6-Phenylbenzo[k]phenanthridine (3r)20f. White solid, iso- 7.6 Hz, 2H), 7.68 (d, J = 8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
lated yield (88 mg, 58%) (for 0.5 mmol),1H NMR (500 MHz, 28.9, 51.4, 55.4, 113.5, 128.0, 128.4, 161.8, 166.4.
DMSO-d6): d 7.57–7.62 (m, 3H), 7.70 (dd, J1 = 6 Hz, J2 = 1 Hz,
N-(tert-Butyl)benzamide (5b)21a,b. White solid, isolated yield
2H), 7.80 (td, J1 = 6 Hz, J2 = 1 Hz, 1H), 7.84 (td, J1 = 5.5 Hz, J2 = (66 mg, 74%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d 1.47
0.5 Hz, 2H) 7.87 (t, J = 6.5 Hz, 2H), 8.06 (d, J = 7.5 Hz, 1H), 8.17 (s, 9H), 6.02 (s, 1H), 7.38 (t, J = 6.4 Hz, 2H), 7.44 (t, J = 6.4 Hz,
(dd, J1 = 6 Hz, J2 = 1.5 Hz, 1H), 8.24 (dd, J1 = 7 Hz, J2 = 1 Hz, 1H), 1H), 7.71 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 28.8,
9.05 (d, J = 7 Hz, 1H), 9.16 (d, J = 6.5 Hz, 1H); 13C NMR (125 51.5, 126.7, 128.4, 131.0, 135.8, 166.9.
MHz, DMSO-d6): d 123.0, 123.2, 124.2, 126.8, 127.1, 127.4,
128.2, 128.2, 128.3, 128.3, 128.3, 128.7, 128.7, 129.8, 129.9, lated yield (71 mg, 69%) (for 0.5 mmol),1H NMR (400 MHz,
N-(tert-Butyl)-3-methoxybenzamide (5c)21a. White solid, iso-
131.5, 134.2, 139.5, 145.1, 159.6.
CDCl3): d 1.46 (s, 9H), 3.83 (s, 3H), 5.95 (s, 1H), 6.98 (dd, J1 =
White 8 Hz, J2 = 2.4 Hz, 1H), 7.20 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.27
6-(4-Bromophenyl)indolo[1,2-a]quinoxaline (3s)20f
.
solid, isolated yield (89 mg, 48%) (for 0.5 mmol),1H NMR (t, J = 8 Hz, 1H), 7.32 (t, J = 2 Hz, 1H); 13C NMR (100 MHz,
(400 MHz, CDCl3): d 7.29 (s, 1H), 7.48 (t, J = 6 Hz, 2H), 7.60 (t, CDCl3): d 28.8, 51.6, 55.4, 112.1, 117.3, 118.4, 129.4, 137.4,
J = 6.5 Hz, 1H), 7.66 (t, J = 6 Hz, 1H) 7.74 (d, J = 7.2 Hz, 2H), 7.95 159.8, 166.7.
(d, J = 7 Hz, 2H), 7.97 (d, J = 7 Hz, 1H), 8.09 (d, J = 6.5 Hz, 1H),
N-(tert-Butyl)-3-methylbenzamide (5d)21a. White solid, isolated
8.54 (d, J = 7.5 Hz, 1H), 8.57 (d, J = 7 Hz, 1H); 13C NMR (100 MHz, yield (70 mg, 73%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d
CDCl3): d 102.3, 114.6, 114.7, 122.8, 122.9, 124.3, 124.4, 124.6, 1.47 (s, 9H), 2.38 (s, 3H), 5.97 (s, 1H), 7.27–7.30 (m, 2H), 7.47–7.50
128.6, 128.8, 129.2, 130.3, 130.6, 131.9, 133.2, 136.2, 137.2, 155.1. (m, 1H), 7.54 (s, 1H); 13C NMR (100 MHz, CDCl3): d 21.3, 28.8,
4-Phenylpyrrolo[1,2-a]quinoxaline (3t)20g. White solid, iso- 51.5, 123.6, 127.4, 128.3, 131.7, 135.8, 138.2, 167.1.
lated yield (76 mg, 62%) (for 0.5 mmol),1H NMR (400 MHz,
3-Bromo-N-(tert-butyl)benzamide (5e)21a. White solid, isolated
CDCl3): d 6.89 (t, J = 3.5 Hz, 1H), 6.99 (d, J = 3.5 Hz, 1H), 7.45 (td, yield (100 mg, 78%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3):
J1 = 6.5 Hz, J2 = 0.5 Hz, 1H), 7.51–7.56 (m, 4H), 7.88 (d, J = 7 Hz, d 1.47 (s, 9H), 5.93 (s, 1H), 7.27 (t, J = 8 Hz, 1H), 7.58 (dt, J1 = 8 Hz,
1H), 7.99–8.01 (m, 3H), 8.04 (dd, J1 = 7 Hz, J2 = 1 Hz, 1H); 13C J2 = 1.2 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.84 (t, J = 2 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d 108.7, 113.6, 113.9, 114.6, 125.3, NMR (100 MHz, CDCl3): d 28.7, 51.9, 122.6, 125.3, 129.9, 130.1,
125.4, 127.2, 127.5, 128.6, 128.6, 129.8, 130.3, 136.3, 134.0, 137.9, 165.4.
138.5, 154.4.
N-(tert-Butyl)-4-fluorobenzamide (5f)21a. White solid, isolated
6-Phenylphenanthridine-8-carbonitrile (3u). White solid, iso- yield (61 mg, 63%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3):
lated yield (94 mg, 67%) (for 0.5 mmol), 1H NMR (400 MHz, d 1.45 (s, 9H), 5.91 (s, 1H), 7.04 (t, J = 8.8 Hz, 2H), 7.69–7.74
CDCl3) d 7.58–7.64 (m, 3H), 7.69–7.72 (m, 2H), 7.74 (td, J1 = 7.6 Hz, (m, 2H); 13C NMR (100 MHz, CDCl3): d 28.8, 45.8, 51.7, 115.3,
J2 = 1.2 Hz, 1H), 7.84 (td, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 8.01 (dd, 115.5, 128.9, 129.0, 132.0, 132.1, 163.2, 165.7, 165.8.
J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 8.27 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H),
N-(tert-Butyl)-3-nitrobenzamide (5g)21c. Pale yellow solid,
8.46 (d, J = 1.6 Hz, 1H), 8.60 (d, J = 8 Hz, 1H), 8.77 (d, J = 8.4 Hz, isolated yield (90 mg, 81%) (for 0.5 mmol),1H NMR
1H); 13C NMR (100 MHz, CDCl3) d 110.6, 122.4, 122.5, 123.6, (400 MHz, CDCl3): d 1.49 (s, 9H), 6.09 (s, 1H), 7.59 (t, J = 8
124.7, 127.8, 128.8, 129.4, 129.7, 130.7, 130.7, 131.7, 134.3, 136.0, Hz, 1H), 8.08 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 8.29–8.32 (m, 1H),
144.7, 160.4; HRMS (ESI-TOF) m/z [M + H]+ calcd for C20H13N2 8.50 (t, J = 2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 28.8, 52.3,
281.1073; found 281.1080.
121.5, 125.7, 129.7, 133.1, 137.5, 148.1, 164.4.
N-Cyclohexylbenzamide (5h)21c. White solid, isolated yield
(47 mg, 46%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d 1.19–
RVC plate 1.28 (m, 3H), 1.39–1.47 (m, 2H), 1.64 (t, J = 4.8 Hz, 1H), 1.73
General procedure for the synthesis of 5
An undivided cell was equipped with
a
(15 mm ꢁ 15 mm ꢁ 5 mm) anode and a platinum plate (dd, J1 = 6.2 Hz, J2 = 3.2 Hz, 2H), 2.01 (t, J = 3.6 Hz, 2H), 3.95–4.03
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(m, 1H), 6.03–6.14 (m, 1H), 7.38–7.50 (m, 3H), 7.74–7.76 (m, 2H); Kumar Baroliya, Department of Chemistry, MLSU for providing
13C NMR (100 MHz, CDCl3): d 24.9, 25.5, 33.2, 48.7, 126.5, 128.5, access to instrument for CV studies.
128.5, 131.2, 135.0, 166.7.
N-Benzylbenzamide (5i)21a. Brown solid, isolated yield (81
mg, 77%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d 4.62 (dd,
J1 = 5.4 Hz, J2 = 2.4 Hz, 2H), 6.58 (s, 1H), 7.27–7.31 (m, 1H), 7.34
References
(d, J = 4.4 Hz, 4H), 7.39 (td, J1 = 7 Hz, J2 = 1.2 Hz, 2H), 7.47 (tt,
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(100 MHz, CDCl3): d 44.1, 126.9, 127.6, 127.9, 128.6, 128.8,
131.5, 134.3, 138.2, 167.4.
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N-(4-Methoxyphenyl)benzamide (5j)21d. Pale yellow solid,
isolated yield (95 mg, 84%) (for 0.5 mmol),1H NMR (400 MHz,
CDCl3): d 3.81 (s, 3H), 6.88 (dt, J1 = 9.2 Hz, J2 = 2.8 Hz, 2H), 7.45
(t, J = 6.8 Hz, 2H), 7.52 (t, J = 1.2 Hz, 1H), 7.53 (d, J = 2.8 Hz, 1H),
7.55 (s, 1H), 7.82 (s, 1H), 7.85 (d, J = 1.6 Hz, 1H), 7.87 (s, 1H); 13
C
NMR (100 MHz, CDCl3): d 55.5, 114.2, 122.1, 126.9, 128.7, 130.9,
131.7, 135.0, 156.6, 165.6.
N-(2,6-Dimethylphenyl)benzamide (5k)21c. White solid, iso-
lated yield (61 mg, 54%) (for 0.5 mmol),1H NMR (400 MHz,
CDCl3): d 2.24 (s, 6H), 7.08–7.16 (m, 3H), 7.44 (d, J = 7.2 Hz, 2H),
7.53 (tt, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.58 (s, 1H), 7.88 (t, J =
1.2 Hz, 1H), 7.90 (s, 1H); 13C NMR (100 MHz, CDCl3): d 18.5,
127.2, 127.4, 128.2, 128.7, 131.7, 133.9, 134.4, 135.6, 165.9.
N-(4-Bromophenyl)benzamide (5l)21e. White solid, isolated
yield (108 mg, 78%) (for 0.5 mmol),1H NMR (100 MHz, CDCl3 +
DMSO): d 7.30–7.40 (m, 5H), 7.57 (d, J = 8.4 Hz, 2H), 7.77 (d, J =
7.2 Hz, 2H), 9.16 (s, 1H); 13C NMR (400MHz, CDCl3 + DMSO): d
116.5, 122.1, 127.6, 128.6, 131.8, 135.1, 138.2, 166.2, 207.1.
N-(2-(3a,7a-Dihydro-1H-indol-3-yl)ethyl)benzamide
(5m)21f
.
Yellow solid, isolated yield (56 mg, 42%) (for 0.5 mmol),1H NMR
(400 MHz, CDCl3): d 3.05 (t, J = 6.8 Hz, 2H), 3.76 (d, J = 5.6 Hz, 2H),
6.43 (s, 1H), 7.00 (s, 1H), 7.08 (t, J = 7.2 Hz, 1H), 7.17 (t, J = 8 Hz,
1H), 7.33 (t, J = 8 Hz, 3H), 7.42 (t, J = 7.2 Hz, 1H), 7.61 (d, J = 8 Hz,
1H), 7.65 (d, J = 7.2 Hz, 2H), 8.43 (s, 1H); 13C NMR (100 MHz,
CDCl3): d 25.2, 40.3, 111.4, 112.7, 118.7, 119.4, 122.1, 122.2, 126.9,
127.2, 128.5, 131.4, 134.4, 136.4, 167.7.
N-(tert-Butyl)isonicotinamide (5n)21g. White solid, isolated
yield (28 mg, 32%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d
1.43 (s, 9H), 6.19 (s, 1H), 7.51 (d, J = 6 Hz, 2H), 8.63 (d, J =
5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 28.6, 52.0, 120.7,
142.8, 150.3, 164.8.
1,10-Biphenyl (6)22. Pale yellow solid, isolated yield (19 mg,
24%) (for 0.5 mmol),1H NMR (400 MHz, CDCl3): d 7.21 (tt, J1 =
7.2 Hz, J2 = 1.2 Hz, 2H), 7.28 (tt, J1 = 7.6 Hz, J2 = 2.4 Hz, 4H),
7.48–7.51 (m, 4H); 13C NMR (100 MHz, CDCl3): d 127.1, 127.5,
129.0, 136.9.
Conflicts of interest
5 M. Tobisu, K. Koh, T. Furukawa and N. Chatani, Angew.
Chem., Int. Ed., 2012, 51, 11363–11366.
6 Z. Xia, J. Huang, Y. He, J. Zhao, J. Lei and Q. Zhu, Org. Lett.,
2014, 16, 2546–2549.
The authors declare no competing financial interest.
7 T. Xiao, L. Li, G. Lin, Q. Wang, P. Zhang, Z. W. Mao and
L. Zhou, Green Chem., 2014, 16, 2418–2421.
Acknowledgements
This work was supported by the grant from the SERB-India,
grant no. SRG/2020/000721. SS sincerely thanks Dr Prabhat
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