Iron pentacarbonyl in alkoxy- and aminocarbonylation of aromatic halides

Article abstract of DOI:10.1055/s-0034-1379227

We have identified reaction conditions for a Heck-type carbonylation based on [Fe(CO)₅]. Preliminary optimization of alkoxycarbonylation on 2-bromonaphthalene defined functioning composition of the reaction mixture which was then applied on a small set of (hetero)aromatic halides. Respective aminocarbonylation of these halides with different amines, including aniline and benzotriazole, was accomplished with reasonable results.

Full text of DOI:10.1055/s-0034-1379227

LETTER
▌2579
lIertteor n Pentacarbonyl in Alkoxy- and Aminocarbonylation of Aromatic Halides
Alkoxy- and Aminocarbonylation of Aromatic Halides
Matej Babjak,* Oľga Caletková, Diana Ďurišová, Tibor Gracza
Department of Organic Chemistry, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia
Fax +421(2)52968560; E-mail: matej.babjak@stuba.sk
Received: 24.06.2014; Accepted after revision: 10.09.2014
Considering the revelations of our predecessors,2 we con-
Abstract: We have identified reaction conditions for a Heck-type
ceived an idea that [Fe(CO)5] in the presence of acidic
carbonylation based on [Fe(CO)5]. Preliminary optimization of
protons (i.e., from MeOH or other protic nucleophile) and
a base could form a reactive hydride–iron complex, capa-
alkoxycarbonylation on 2-bromonaphthalene defined functioning
composition of the reaction mixture which was then applied on a
small set of (hetero)aromatic halides. Respective aminocarbonyla- ble of a selective reductive cleavage of the iodine from the
tion of these halides with different amines, including aniline and
benzotriazole, was accomplished with reasonable results.
aromatic ring, similarly to the transformation, reported by
Brunet5 (Scheme 1), based on the combination of potassi-
Key words: aminocarbonylation, methoxycarbonylation, carbon-
ylation, carbonyl complexes, iron, palladium catalysis
um carbonate and methanol. What was important for our
plans, in situ formed iron hydride is too weak to harm oth-
er halogens (e.g., bromo or chloro substituents) or other
reducible functional groups.
Heck carbonylation1 represents a powerful alternative to
other metalation-based transformations of aryl and het-
eroaryl halides to the corresponding carboxylates and car-
boxamides, such as lithiation followed by cyanoformate
or carbon dioxide addition. Unfortunately, the reaction in
its traditional form requires a presence of gaseous CO at
high pressure, and as such invokes serious safety appre-
hensions. Therefore, several surrogates of CO have been
introduced during last years, namely pivaloyl chloride,2a
DMF2b or formates.2c Along with these methods, use of
various metal carbonyls, particularly [Mo(CO)6],2e–i,2m
[Cr(CO)6],2j and [W(CO)5]2j–l was reported with excellent
results.
[Fe(CO)5] (18 mol%)
K2CO3 (2.1 equiv), MeOH
60 °C, 2–48 h
X
H
X
I
>70%
X = 4-Br, 4-Cl, 3-Cl
2-Cl, 4-I
O
MeO–
[HFe(CO)4]–
+
[Fe(CO)5]
+
MeOH
MeO
OMe
Scheme 1 Selective reduction of iodides with [Fe(CO)5]5
Here we presumed that the reaction of iodotoluene, stud-
ied by Larhed, afforded through similar reduction the tol-
uene, which was then neglected in the toluene solution. In
the analogy with the described Brunet reduction, we be-
lieved that reductive properties of carbonyl–iron hydrides
are insufficient for the removal of the bromo substituent
from the aromatic ring and at the same time, aryl bromides
are well qualified to undergo the Heck carbonylation.
Therefore we decided to repeat the Larhed experiment on
selected aromatic bromides.6
When pioneering this field, Larhed and co-workers made
an early-stage finding that affordable carbonyls, such as
[Fe(CO)5] or [Ni(CO)4], were unable to carbonylate the
model substrate, 4-iodotoluene. Also Oshima and co-
workers3 had tested the precondition that [Fe(CO)5] fails
as a CO supply for the Heck carbonylation of iodides, and
they identified [CpFe(CO)2]2 to be the optimal reagent for
the task.
Our initial model substrate was the 2-bromonaphthalene
(1), as a cheap, solid, electron-rich substrate. Original
conditions for the Heck methoxycarbonylation of bromo-
benzenes were chosen as the starting point, comprising 10
mol% of Pd(OAc)2, 20 mol% of Ph3P, triethylamine and
methanol as cosolvent (Scheme 2).7 Initial procedure was
performed with one equivalent of iron pentacarbonyl.
On the other hand, it is worth to note that [Fe(CO)5] is the
cheapest metal carbonyl compound available, produced in
bulk scale (e.g., 9000 t/year by BASF),4 liquid, nonvola-
tile, easy to handle, air and solution stable. Vapors of the
compound are detectable by its characteristic odor, in con-
trast to odorless CO. Toxicity of metal carbonyls is in pro-
portion with their volatility; in case of [Fe(CO)5] (bp
105 °C at 1.013 bar) it is though reduced if compared with
free CO or [Ni(CO)4], but higher than the toxicity of solid
carbonyls, for example, [Mo(CO)6] or [W(CO)6]. On the
other hand, use of [Mo(CO)6] or [W(CO)6] introduces an-
other toxic metal to the reaction environment in contrast
with nontoxic iron.
Fe(CO)5 (X mol%)
Br
COOMe
Pd catalyst (10 mol%)
phosphine Y
base Z
1
2
MeOH + cosolvent
80 °C
Scheme 2 Model methoxycarbonylation with [Fe(CO5)]
SYNLETT 2014, 25, 2579–2584
Advanced online publication: 15.10.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1379227; Art ID: st-2014-b0535-l
© Georg Thieme Verlag Stuttgart · New York

2580
M. Babjak et al.
LETTER
In the next step, the optimal reaction conditions were will be lower than for the unopened run.7 This can be sim-
sought through the thorough variation of reaction condi- ply explained by the escape of certain amount of free CO
tions.7 The amount of [Fe(CO)5] was reduced to 25 mol%, from the vessel. Therefore, an appropriate reaction time
similarly to the published use of [Mo(CO)6] or [Cp- for each substrate must be determined iteratively, in our
Fe(CO)2]2. Acetonitrile was chosen as the optimal cosol- case, reactions of most substrates required equally 23
vent and trialkyl amines, for example, triethylamine and hours reaction time.
DIPEA as the base. Pd(OAc)2 was found to be the best
Thus, our optimized conditions for the methoxycarbon-
supply of palladium. As a phosphine additive, Ph3P and
ylation of 2-bromonaphthalene comprise 10 mol% of
especially 1,1′-bis(diphenylphosphino)ferrocene (dppf)
Pd(OAc)2, 25 mol% of [Fe(CO)5], 36 mol% of phosphine,
were qualified as the best ones, but it was essential to use
10 equivalents of Et3N, and heating at 80 °C in MeOH–
it in amount at least of 36 mol%. This finding evoked sim-
MeCN. In comparison with similar methods, formation of
ple hypothesis that at least one phosphine chelates the iron
methyl 2′-naphthoylformate,8a–c binaphtylketone or
atom, releasing the CO from the ligand field. This hypoth-
binaphthalene8d–f was not observed. These conditions
esis was then supported by the standalone reaction of Ph3P
were then used in the preparative manner for the transfor-
and [Fe(CO)5] in stoichiometric ratio in MeCN–Et3N.7
mation of 2-bromopyridine and 3-bromoquinoline to the
Considering the known ability of iron compounds to un-
corresponding methylcarboxylates (Table 1, entries 2 and
dergo aryl bromine oxidative insertion, we have per-
3). In the case of 2-bromopyridine, small amount of bipyr-
formed a control experiment without palladium catalyst,
idine was observed in the reaction mixture by LC–MS.
but with negative results. Small-scale experiments (0.1
Interestingly, switching from MeOH in MeCN to neat
mmol) with LC–MS monitoring were used for the initial
n-BuOH9 led to further improvement, and in this case
optimization on 2-bromonaphthalene. A scaled-up reac-
Ph3P was a quite acceptable additive.
tion (1 mmol) under the optimized conditions with Ph3P
Rather mixed results in the oxycarbonylation series ori-
ented us more towards the analogous aminocarbonyla-
tions, where we see the major potential of the method. In
revealed that the isolated yield of 2 is lower than the
HPLC estimation, mostly due to permanent interference
of triphenylphosphine oxide and 2 during the flash chro-
this case, all tested halides including heteroaryl bromides,
matography (Ph3P immobilized on polystyrene resin was
such as 2-bromopyridine or bromoquinolines, furnished
the corresponding amides in good yield, especially with
reactive benzylamine (Table 2). Yields were seemingly
independent from electron density on the aromatic ring of
the bromide. ortho-Substituted bromide furnished an ap-
propriate carbonylation product (Table 2, entry 8) as well.
The cyclic amidine product 23, isolated from the reaction
of 2-bromonitrile 21, was little surprising in the first mo-
tried without success7). To avoid this, the use of dppf was
tested with positive results, bringing shorter reaction time
as enjoyable bonus. The reaction with dppf furnished then
the methylester 2 in 71% isolated yield after four hours
(Table 1, entry 1).
It was found that the reaction can be interrupted (opened,
analyzed, reclosed, and further heated), but the final yield
Table 1 Carbonylation of Aryl Halidesa
Entry
Bromide
Productb
Byproduct
Yield (%)d
Yield (%)e
COOR
Br
2 36
3 52
1
2 71
2 R = Me
3 R = n-Bu
1
N
COOR
N
Br
N
5 (80) 6
6 39
7 (13)
5 (90) 25
7 (10)
2
3
N
5 R = Me
6 R = n-Bu
7c
4a
8
N
N
COOR
9 40
10 87
Br
9 R = Me
10 R = n-Bu
a The reactions were carried out as described in the general procedure.11
b Isolated yields; yields in parentheses are estimated yields (HPLC).7
c Compound 7 was observed only in reactions with MeOH.
d With dppf as phosphine additive.
e With Ph3P as phosphine additive.
Synlett 2014, 25, 2579–2584
© Georg Thieme Verlag Stuttgart · New York

LETTER
Alkoxy- and Aminocarbonylation of Aromatic Halides
2581
ment, but its formation is logical and already known.10 As
can be seen from entry 6 (Table 2), also an active het-
eroaryl chloride is capable to undergo the reaction. Naph-
thoylbenzotriazole 32 and anilides 12 and 18 represent
then examples of products with unreactive amines. In the
entire aminocarbonylation part, cheap Ph3P was used in-
stead of the dppf, with little disadvantage of extended re-
action time in some cases. Nevertheless for less reactive
bromide or amine part, the use of dppf is always an option.
Buchwald–Hartwig reaction products were not observed
during LC–MS analysis of the reaction mixtures.
Table 2 Overview of Aminocarbonylations with Various Aryl Bro-
midesa,11 (continued)
Entry Bromide
Amine
Product (%)
NH
CN
NH2
Br
N
Bn
8
O
13
22
23 71
Br
HN Bn
NH2
NC
Table 2 Overview of Aminocarbonylations with Various Aryl Bro-
9
O
NC
midesa,11
13
13
25 86
MeO
24
Entry Bromide
Amine
Product (%)
Br
HN Bn
O
NH2
O
O
O
10
MeO
Br
Br
Br
NH2
Ph
Bn
N
H
27 51
26
1
O
N
N
Br
NH2
1
11
13
Bn
N
N
12 80
14 84
N
H
11
12
13
NH2
13
13
28
N
H
29 87
2
NH2
H
1
N
Bn
Br
Br
O
O
N
H
8
1
NEt2
30 63
32 36
3
N
N
H
N
15
1
N
16 43
N
O
N
N
N
N
Br
N
N
H
31
NEt2
4
5
a The reactions were carried out as described in references and notes.11
Specified yields are after isolation.
15
4a
4a
17 77
O
O
Br
NH2
Ph
N
In summary, we have developed a carbonylation method
based on iron pentacarbonyl, in spite of implication, that
this reagent represents unsuitable CO supply for the Heck-
type carbonylation. LC–MS-monitored optimization of
methoxycarbonylation of the 2-bromonaphthalene de-
fined reasonable reaction conditions which were then ap-
plied on few aromatic bromides. In comparison with
methoxycarbonylation, the butoxycarbonylation of these
substrates was found to be slightly more practical. Similar
aminocarbonylations of these bromides with different
amines, including unreactive aniline and benzotriazole,
were accomplished with good results. A successful ami-
nocarbonylation with heteroaromatic chloride was
achieved as well.
N
H
11
13
18 71
X
Bn
N
NH2
N
H
6
7
4a X = Br
4b X = Cl
19 46 (from 4a, 32% from
4b)
O
NH2
Bn
N
Br
N
H
N
20
13
21 62
Acknowledgment
This work was supported by Slovak Grant Agencies (VEGA No.
1/0488/14, APVV-0203-10 and ASFEU, Bratislava, ITMS projects
No. 26240120001, 26240120025).
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2579–2584

2582
M. Babjak et al.
LETTER
corresponding amine (1.5 mmol). Neat iron pentacarbonyl
(35 μL, 0.25 mmol) was added, and the vial was thoroughly
closed and heated in the preheated oil bath or aluminum
heating block (80 °C). The reaction mixture was stirred at
the specified temperature for 23 h, then concentrated with
approximately 1 g of silica, and the absorbed material was
purified by gradient MPLC (hexanes–EtOAc in ratios 1:10
to 1:1). Methyl and n-butyl carboxylates, described in the
article, were prepared in a similar manner; a mixture of
MeCN with MeOH or n-BuOH in a ratio of 2:1 was used
instead of pure MeCN, the identical amount of dppf (0.36
mmol) was used instead of Ph3P in specified cases.
Methyl Naphthalene-2-carboxylate (2)
The compound was prepared according to the described
general procedure with dppf as the ligand additive from 2-
bromonaphthalene (1, 1.035 g, 5 mmol) of, isolated as a
colorless oil (661 mg, 71%). All data, including 1H NMR,
13C NMR, LC–MS, and TLC data were identical with
physical sample of 2, purchased from Sigma-Aldrich.
n-Butyl Naphthalene-2-carboxylate (3)
Supporting Information for this article is available online
at http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
References and Notes
(1) (a) Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem.
1974, 39, 3318. (b) Schoenberg, A.; Bartoletti, I.; Heck, R.
F. J. Org. Chem. 1974, 39, 3327. (c) Barnard, C. F. J.
Organometallics 2008, 27, 5402.
(2) (a) Hermange, P.; Linhardt, A. T.; Taaning, R. H.;
Bjerglund, K.; Lupp, D.; Skydstrup, T. J. Am. Chem. Soc.
2011, 133, 6061. (b) Wan, Y. Q.; Alterman, M.; Larhed, M.;
Hallberg, A. J. Org. Chem. 2002, 67, 6232. (c) Morimoto,
T.; Kaikuchi, K. Angew Chem. Int. Ed. 2004, 43, 5580.
(d) Ueda, T.; Konishi, H.; Manabe, K. Org. Lett. 2013, 15,
5370. (e) Kaiser, N. F. K.; Hallberg, A.; Larhed, M. J. Comb.
Chem. 2002, 4, 109. (f) Georgsson, J.; Hallberg, A.; Larhed,
M. J. Comb. Chem. 2003, 5, 350. (g) Lagerlund, O.; Larhed,
M. J. Comb. Chem. 2006, 8, 4. (h) Letavic, M. A.; Ly, K. S.
Tetrahedron Lett. 2007, 48, 2339. (i) Odell, L. R.;
Savmarker, J.; Larhed, M. Tetrahedron Lett. 2008, 49, 6115.
(j) Wannberg, J.; Larhed, M. J. Org. Chem. 2003, 68, 5750.
(k) Roberts, B.; Liptrot, D.; Alcaraz, L.; Luker, T.; Stocks,
M. J. Org. Lett. 2010, 12, 4280. (l) Wieckowska, A.;
Fransson, R.; Odell, L. R.; Larhed, M. J. Org. Chem. 2011,
76, 978. (m) Wei, R.; Motoki, Y. J. Org. Chem. 2010, 64,
8410.
(3) Nakaya, R.; Yorimitsu, H.; Oshima, K. Chem. Lett. 2011, 40,
904.
(4) Wildermuth, E.; Stark, H.; Friedrich, G.; Ebenhöch, F. L.;
Kühborth, B.; Silver, J.; Rituper, R. Iron Compounds,
Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-
VCH: Weinheim, 2000.
(5) (a) Brunet, J.-J.; Taillefer, M. J. Organomet. Chem. 1988,
348, C5. (b) Brunet, J.-J.; Kindela, F. B.; Neibecker, D.
J. Organomet. Chem. 1989, 368, 209.
(6) Babjak, M.; Karlubíková, O.; Gracza, T. 14th Blue Danube
Symposium on Heterocyclic Chemistry Podbanské 2011
(Book of Abstracts); STU: Bratislava, 2011, 34.
(7) See the Supporting Information.
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 1
(150 mg, 0.72 mmol), isolated as an off-white solid (164 mg,
52%). 1H NMR, 13C NMR, IR, ESI-MS, and TLC data of
isolated 3 were in accordance with published data;12a mp 40–
45 °C (EtOAcOEt); lit.:12b mp 41 °C.
Methyl Pyridine-2-carboxylate (5)
The compound was prepared according to the described
general procedure with dppf as the ligand additive from 2-
bromopyridine (4a, 150 mg, 0.95 mmol), isolated as a pale
yellow oil (33 mg, 25%). HPLC yield in the reaction mixture
was 90% according to the 254 nm peak-area calibration
curve made from purchased sample. All data, including 1H
NMR, 13C NMR, LC–MS, and TLC data were identical with
physical sample of 5, purchased from Sigma-Aldrich. The
isolated sample was slightly colored in contrast with
colorless commercial one.
n-Butyl Pyridine-2-carboxylate (6)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 4a
(150 mg, 0.95 mmol), isolated as a pale yellow oil (66 mg,
39%). All data, including 1H NMR, 13C NMR, IR, ESI-MS,
and TLC data were in accordance with the literature data.13
Methyl Quinoline-3-carboxylate (9)
The compound was prepared according to the described
general procedure with dppf as the ligand additive from 3-
bromoquinoline (8, 250 mg, 1.2 mmol), isolated as an off-
white solid (90 mg, 40%). NMR and IR data were identical
with the literature data;14 mp 74–77 °C (EtOAc–hexanes);
lit.:14 mp 75–77 °C.
(8) For the formation of 2′-aroyl formates via Heck reaction,
see, for example: (a) Sakakura, T.; Yamashita, H.;
Kobayashi, T.; Hayashi, T.; Tanaka, M. J. Org. Chem. 1987,
52, 5733. (b) Ozawa, F.; Kawasaki, N.; Yamamoto, T.;
Yamamoto, A. Chem. Lett. 1985, 567. (c) Tanaka, M.;
Kobayashi, T.; Sakakura, T. J. Chem Soc., Chem. Commun.
1985, 12, 837. For the formation of diaryl ketones and
diarenes under carbonylation conditions, see, for example:
(d) Brunet, J. J.; Zaizi, A. E. J. Organomet. Chem. 1995,
486, 275. (e) Brunet, J.-J.; Zaizi, A. E. Bull. Soc. Chim. Fr.
1996, 133, 75. (f) Brunet, J. J.; Taillefer, M. J. Organomet.
Chem. 1989, 361, C1.
n-Butyl Quinoline-3-carboxylate (10)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 8
(146 mg, 0.7 mmol), isolated as a thick yellow oil (140 mg,
87%). 1H NMR, 13C NMR, and IR data were in accordance
with the literature data.14
(9) Jayasree, S.; Seayad, A.; Gupte, S. P.; Chaudhari, R. V.
Catal. Lett. 1999, 58, 213.
(10) For spontaneous formation from N-benzyl-2-
cyanobenzamide, see: (a) Valters, R. E.; Bace, A. E.;
Valters, S. P. Latvijas PSR Zinatnu Akademijas Vestis,
Kimijas Serija 1972, 726. For physical and spectral
characteristics of 22, see: (b) Beaume, A.; Courillon, C.;
Derat, E.; Malacria, M. Chem. Eur. J. 2008, 14, 1238.
(11) General Procedure for the Carbonylation of Aryl
Halides
N-Phenyl-2-naphthamide (12)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromonaphthalene (1, 207 mg, 1 mmol), isolated as an off-
white solid (198 mg, 80%); mp 166–168 °C (EtOAc); lit.:15b
170–171 °C. 1H NMR (300 MHz, CDCl3): δ = 7.16 (br t, 1
H, J = 7.4 Hz), 7.38 (br t, 2 H, J = 7.9 Hz), 7.51–7.62 (m, 2
H), 7.70 (d, 2 H, J = 7.7 Hz, Ph), 7.85–7.95 (m, 4 H), 8.07
(br s, 1 H), 8.36 (s, 1 H). 13C NMR (75 MHz, CDCl3):
δ = 120.3, 123.5, 124.6, 126.9, 127.5, 127.8, 127.9, 128.7,
128.9, 129.1 (all d), 132.2, 132.6, 134.8, 138.0 (all s), 165.8
An aryl bromide (1 mmol), Ph3P (94 mg, 0.36 mmol), and
Pd(OAc)2 (22 mg, 0.1 mmol) were weighed into screw cap
vial equipped with a magnetic stir bar. Dry MeCN (5 mL)
was added, followed by Et3N (2.5 mL) and the
Synlett 2014, 25, 2579–2584
© Georg Thieme Verlag Stuttgart · New York

LETTER
(s). IR spectra were in agreement with the literature data.15a
Alkoxy- and Aminocarbonylation of Aromatic Halides
2583
δ = 4.61 (d, 2 H, J = 5.7 Hz), 6.82 (br s, 1 H), 7.17–7.38 (m,
5 H), 7.67 (d, 2 H, J = 8.1 Hz), 7.87 (d, 2 H, J = 8.1 Hz), in
fair accordance with the literature data.21a 13C NMR (75
MHz, CDCl3): δ = 44.3 (t), 115.0, 117.9 (all s), 127.2, 127.7,
127.8, 128.6, 128.8, 132.3 (all d), 137.5, 138.2 (all s), 165.6
(s). IR (ATR): ν = 3309, 3030, 2233, 1643, 1548, 1494,
1311, 719, 672 cm–1. ESI-HRMS: m/z calcd for C15H12N2O
+ H [M + 1]: 237.1022; found: 237.1018.
NMR in DMSO can be found there as well. ESI-HRMS: m/z
calcd for C17H13NO + H [M + 1]: 248.1070; found:
248.1078.
N-Benzyl-2-naphthamide (14)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromonaphthalene (1, 207 mg, 1 mmol), isolated as an off-
white solid (220 mg, 84%). Spectral data (NMR, IR, MS)
were in agreement with the literature data;2m mp 140–142 °C
(EtOAc); lit.:15a mp 138–139 °C.
N-Benzyl-4-methoxybenzamide (27)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 4-
bromoanisole (26, 187 mg, 1 mmol), isolated as a white solid
(123 mg, 51%). Spectral data were in accordance with the
literature data;2m mp 128–130 °C (EtOAc–hexanes); lit.22
mp 129–130 °C.
N,N-Diethyl-2-naphthamide (16)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromonaphthalene (1, 207 mg, 1 mmol), isolated as a thick
colorless oil (98 mg, 43%). All NMR and IR data were in
accordance with the literature data.16
N-Benzylquinoline-2-carboxamide (29)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromoquinoline (28, 208 mg, 1 mmol), isolated as a white
solid (228 mg, 87%). Spectral data were in full accordance
with the literature data;2m mp 125–127 °C (EtOAc); lit.:2m
124–125 °C.
N,N-Diethylpicolinamide (17)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromopyridine (4a, 158 mg, 1 mmol), isolated as a pale
yellow oil (137 mg, 77%). All properties were in full
accordance with the literature data.17
N-Benzylquinoline-3-carboxamide (30)
N-Phenyl-2-pyridinecarboxamide (18)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 3-
bromoquinoline (8, 208 mg, 1 mmol), isolated as a white
solid (165 mg, 63%); mp 140–141 °C (EtOAc); lit.:2c
140 °C. NMR and IR data were in rough agreement with the
literature data.2c 1H NMR (300 MHz, CDCl3): δ = 4.69 (d, 2
H, J = 5.7 Hz), 6.94 (br s, 1 H), 7.22–7.40 (m, 5 H), 7.58
(ddd, 1 H, J = 1.0, 7.0, 8.0 Hz), 7.77 (ddd, 1 H, J = 1.4, 7.0,
8.4 Hz), 7.83 (br d, 1 H, J = 8.1 Hz, H-5), 8.10 (br d, 1 H,
J = 8.4 Hz), 8.59 (br d, 1 H, J = 2.0 Hz), 9.26 (d, J = 2.2 Hz).
13C NMR (75 MHz, CDCl3): δ = 44.2 (t), 126.8 (s), 127.5 (d),
127.7 (d), 128.0 (s), 128.7, 128.8, 129.3, 131.2, 135.6 (all d),
137.8 (s), 148.1 (d), 149.2 (s), 165.5 (s). IR (ATR): ν = 3257,
3059, 3028, 1659, 1620, 1542, 1500, 1430, 1302, 1250 740,
692 cm–1. ESI-HRMS: m/z calcd for C17H14N2O + H [M + 1]:
263.1179; found: 263.1170.
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 4a
(158 mg, 1 mmol), isolated as a yellowish solid (141 mg,
71%). All spectral data were in accordance with the
literature data;18a mp 74–76 °C (EtOAc–hexanes); lit.18b mp
74–75 °C.
N-Benzyl-2-pyridinecarboxamide (19)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from
bromide 4a (158 mg, 1 mmol) or from chloride 4b (114 mg,
1 mmol), isolated in both cases as a pale brown solid (98 mg,
46% from bromide 4a, 68 mg, 32% from chloride 4b). All
spectral data were in agreement with the literature data;19 mp
81–83 °C (EtOAc–hexanes); lit.19 mp 81–84 °C.
N-Benzyl-4-pyridinecarboxamide (21)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 4-
bromopyridine (20, 158 mg, 1 mmol), isolated as an off-
white solid (132 mg, 62%); mp 86–88 °C (EtOAc–hexanes;
lit.20b mp 87–88 °C.
1-(2-Naphthoyl)benzotriazole (32)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from
naphthalene 1 (207 mg, 1 mmol), isolated as a pale brown
solid (98 mg, 36%). Spectral data were in full agreement
with the literature data;23a mp 137–139 °C (EtOAc); lit.23b
mp 140–142 °C.
1H NMR (300 MHz, CD3OD): δ = 4.58 (s, 2 H), 7.34 (br s,
5 H), 7.82 (br s, 2 H), 8.71 (br s, 2 H), in rough agreement
with the literature data.20a 13C NMR (75 MHz, CD3OD):
δ = 44.7 (t), 123.2 (d, 2 C), 128.4, 128.7, 129.6 (all d), 139.7
(s), 143.9 (s), 151.0 (d, 2 C), 167.6 (s). IR (ATR): ν = 3300,
3064, 1645, 1542, 1196, 1172, 1126, 723, 660 cm–1. ESI-
HRMS: m/z calcd for C13H12N2O + H [M + 1]: 213.1022;
found: 213.1018.
(12) (a) Chan, A.; Maki, B. E.; Phillips, E. M.; Scheidt, K. A.
Org. Lett. 2007, 9, 371. (b) Arrowsmith, G. B.; Jeffery, G.
H.; Vogel, A. I. J. Chem. Soc. 1965, 2072.
(13) Beller, M.; Maegerlein, W.; Indolese, A. F.; Fischer, C.
Synthesis 2001, 1098.
(14) Kim, H. J.; Jeong, E. M.; Lee, K.-J. J. Heterocycl. Chem.
2011, 48, 965.
2-Benzyl-3-iminoisoindolin-1-one (23)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 2-
bromobenzonitrile (22, 182 mg, 1 mmol), isolated as an off-
white solid (168 mg, 71%); mp 123–124 °C (EtOAc); lit.10b
mp 122–123 °C. NMR spectra were in accordance with the
literature data.10b IR spectra were in accordance with the
literature.10a ESI-HRMS: m/z calcd for C15H12N2O + H [M +
1]: 237.1022; found: 237.1019.
(15) (a) Gonec, T.; Bobal, P.; Sujan, J.; Pesko, M.; Guo, J.;
Kralova, K.; Pavlacka, L.; Vesely, L.; Kreckova, E.; Kos, J.;
Coffey, A.; Kollar, P.; Imramovsky, A.; Placek, L.;
Jampilek, J. Molecules 2012, 17, 613. (b) Collington, D. M.;
Hey, D. H.; Rees, C. W. J. Chem. Soc. C 1968, 1017.
(16) Niko, Y.; Hiroshige, Y.; Kawauchi, S.; Konishi, G.-I. J. Org.
Chem. 2012, 77, 3986.
(17) Wang, X.; Wang, D.-Z. Tetrahedron 2011, 67, 3406.
(18) (a) Takács, A.; Jakab, B.; Petz, A.; Kollár, L. Tetrahedron
2007, 63, 10372. (b) Wang, Y.; Zhu, D.; Tang, L.; Wang, S.;
Wang, Z. Angew. Chem. Int. Ed. 2011, 50, 8917.
(19) Gou, F.-R.; Wang, X.-C.; Huo, P.-F.; Bi, H.-P.; Guan, Z.-H.;
Liang, Y.-M. Org. Lett. 2009, 11, 5726.
N-Benzyl-4-cyanobenzamide (25)
The compound was prepared according to the described
general procedure with Ph3P as the ligand additive from 4-
bromobenzonitrile (24, 182 mg, 1 mmol), isolated as an off-
white solid (203 mg, 86%); mp 150–153 °C (EtOAc–
hexanes); lit.21b mp 151 °C. 1H NMR (300 MHz, CDCl3):
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2579–2584

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M. Babjak et al.
LETTER
(20) (a) Epsztajn, J.; Bieniek, A.; Plotka, M. W. J. Chem. Res.
1986, 1, 442. (b) Kim, B. R.; Lee, H.-G.; Kang, S.-B.; Sung,
G. H.; Kim, J.-J.; Park, J. K.; Lee, S.-G.; Yoon, Y.-J.
Synthesis 2012, 44, 42.
(21) (a) Toshikatsu, M.; Kazuaki, I.; Hisashi, Y. Org. Lett. 2005,
7, 5043. (b) Ueda, T.; Konishi, H.; Manabe, K. Org. Lett.
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(22) Martinelli, J. R.; Clark, T. P.; Watson, D. A.; Munday, R. H.;
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(23) (a) Katritzky, A. R.; Tala, S. R.; Abo-Dya, N. E.; Gyanda,
K.; El-Gendy, B. E.-D. M.; Abdel-Samii, Z. K.; Steel, P. J.
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M.; Todadze, E.; Khelashvili, L.; El-Feky, S. A.; Katritzky,
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Synlett 2014, 25, 2579–2584
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