Synthesis of brominated bisamides and their application to the suzuki coupling

Article abstract of DOI:10.1016/j.molstruc.2018.05.103

Two brominated bisamides were developed by this protocol. Compounds were synthesized either by 4-bromobenzoyl chloride and ethylenediamine or by ortho-phenylenediamine. The choice of the diamine led to the desired products, which were characterized by IR,

Full text of DOI:10.1016/j.molstruc.2018.05.103

Accepted Manuscript
Synthesis of brominated bisamides and their application to the suzuki coupling
Sabrina M. Nobre, Valeria M.S. Cavalheiro, Leonardo L. Duarte
PII:
S0022-2860(18)30682-3
10.1016/j.molstruc.2018.05.103
MOLSTR 25276
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 26 January 2018
Revised Date: 28 May 2018
Accepted Date: 29 May 2018
Please cite this article as: S.M. Nobre, V.M.S. Cavalheiro, L.L. Duarte, Synthesis of brominated
bisamides and their application to the suzuki coupling, Journal of Molecular Structure (2018), doi:
10.1016/j.molstruc.2018.05.103.
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SYNTHESISOFBROMINATED BISAMIDES ANDTHEIR APPLICATION TO THE
SUZUKI COUPLING
a
∗
a
a
Sabrina M. Nobre , Valéria M. S. Cavalheiro , Leonardo L. Duarte
a
Escola de Química e Alimentos, Universidade Federal do Rio Grande, Av. Itália,
km 08, Campus Carreiros, 96203-900, Rio Grande, RS, Brazil
Tel. no.: +55 53 33326963, fax no.: +55 53 33326960
Corresponding author. Tel. no.: +55 53 33326963; fax no.: +55 53 33326960
E-mail address: sabrinanobre@furg.br (Nobre, S.M)
ABSTRACT
Two brominated bisamides were developed by this protocol. Compounds were synthesized
either by 4-bromobenzoyl chloride and ethylenediamine or by ortho-phenylenediamine. The choice
of the diamine led to the desired products, which were characterized by IR, 1H NMR, 13C NMR and
XRD techniques.
Compounds were applied to the Suzuki coupling. They were efficient for bromides with
activating and deactivating substituent groups. In the reaction performed at low temperature and in
short time, with yields over 95%, it was fundamental to choose the palladium source.
Keywords: Bisamide synthesis, palladium, Suzuki couplings, bisamide characterization
1 - INTRODUCTION
In the last decades, researchers have been studying new catalytic systems, such as the
synthesis of catalysts and auxiliary ligands in the search for simpler processes with less waste
generation and fewer pollutants. There has also been industrial interest in developing systems that
apply to a wide variety of substrates [1,2,3].
1

The Suzuki coupling is an important reaction since it is applied to various areas in
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Chemistry, such as the synthesis of natural polymeric pharmaceuticals [4-9]. In this coupling,
palladium complexes, either with or without auxiliary ligands, are catalytic systems [10]. The class
of compounds which acts with the palladium auxiliary ligand is broad; it comprises mainly
phosphines, carbenes, guanidines, imines, iminophosphines, oximes and bisamides [11-18].
However, there has been need to develop new auxiliary ligands for the catalytic system to be
applied to aryl halides with different substituents, with either aromatic ring activators or
deactivators, as well as an efficient system for chlorides.
Bisamides are organic, peptidomimetic and biologically active compounds. This class of
compounds has already been applied to catalysis as auxiliary ligands of palladium complexes
[19,20]. However, they have been scarcely applied to coupling reactions, even though they proved
to be very efficient in Suzuki reactions [21,22]. In the study carried out by Nobre et al., bisamides
acted as ligands of palladium acetate in the coupling between aryl halides and arylboronic acids.
The reaction occurred at room temperature in short time with no use of any inert atmosphere [21].
In this study, in addition to synthesizing and characterizing two new brominated bisamides, the
evaluation of the influence of the bromine substituent and the nitrogen separating group on the
bisamide molecule was carried out.
To extend the scope of use of these compounds as palladium auxiliary ligands applied to the
Suzuki coupling, this protocol reports the synthesis and characterization of new bisamides, besides
their application to the Suzuki coupling.
2 - EXPERIMENTAL
2.1 - Synthesis of bisamide 1,2-bis(4-bromobenzamide)benzene [21]
The synthesis of this compound was carried out by 4-bromobenzoyl chloride (5mmol, 1.1g)
and triethylamine (5 mmol, 0.7 mL), together with ortho-phenylenediamine (2.5 mmol, 0.25g) and
2

methylene chloride (20 mL). The system was maintained under magnetic stirring at 25 ºC for 20h.
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Afterwards, the solvent was removed and the resulting solid was crystallized from
dimethylsulfoxide. The purified product, whose melting point was 262 ºC, was characterized by
infrared spectroscopy, proton and carbon nuclear magnetic resonance and X-ray diffraction. Yield
was 89%.
2.2 - Synthesis of bisamide 1,2-bis (4-bromobenzamide)ethane [21]
The synthesis of this compound was carried out by 4-bromobenzoyl chloride (5mmol; 1.1g)
in 10 mL methylene chloride, together with ethylenediamine (2.5 mmol; 0.165 mL) and
triethylamine (5 mmol; 0.7 mL). The system was maintained under magnetic stirring at 25 ºC for
20 h. Afterwards, the solvent was removed and the resulting solid was crystallized from
dimethylsulfoxide. The purified product, whose melting point was 210 ºC, was characterized by
infrared spectroscopy, proton and carbon nuclear magnetic resonance and X-ray diffraction. Yield
was 90%.
2.3 – Catalytic Suzuki coupling reactions [21]
In this experiment, an oven-dried resealable Schlenk flask was filled with [Pd] (0.01 mmol),
ligand (0.03 mmol), aryl halides (1.0 mmol), arylboronic acid (1.5 mmol), K2CO3 (2 mmol) and
EtOH/H2O (6 mL, 1:1) at 70ºC. The reaction mixture was stirred at the desired temperature for 2h.
After that, the solution was taken up in ether (30 mL), washed with aqueous NaOH (1 M, 2 × 5
mL) and brine (2 × 5 mL), and dried over MgSO4. After purification by flash chromatography, the
biphenyl product was characterized by 1H and 13C NMR.
3

3 - RESULTS AND DISCUSSION
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This study aimed at contributing to the development of new catalytic systems by
synthesizing two bisamide compounds which were applied to the Suzuki coupling after
characterization.
Bisamides were synthesized by the reaction between 4-Bromobenzoyl chloride and the
diamine which corresponded to the desired compound (Scheme 1). These reactions, whose solvent
was dichloromethane and whose deprotonating agent was triethylamine, were carried out at room
temperature.
Scheme 1: Synthesis of 1,2-bis(4-bromobenzamide)benzene (Bisamide 1) and 1,2-bis (4-
bromobenzamide)ethane (Bisamide 2)
Initially, bisamides were characterized by infrared spectroscopy [23]. Compounds showed a
strong band in the 3270 cm-1 region. It was attributed to νNH; thus, it indicates the development of
the bisamide. Amide carbonyl was also identified as a strong band around 1649 and 1633 cm-1.
These values are in agreement with the literature [23-25]. Table 1 shows the comparison among the
4

main bands obtained for the synthesized bisamides and bisamides found in the literature. (spectra in
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the supplementary material)
Table 1. Comparison among the main bands found in the literature
This study
Literature [21]
Stretching
of groups
NH
Bisamide 1 Bisamide 2 1,2 bis(benzamide)etane 1,2 bis(benzamide)benzene
(cm-1)
3270
1649
3030
2984
(cm-1)
3277
1633
3069
2977
(cm-1)
3392
1641
3061
2955
(cm-1)
3296
1632
3062
2960
C=O
Carom.-H
Calif.-H
1
The H NMR spectrum of both compounds was obtained in DMSO-d6 at 400 MHz. The
spectrum of Bisamide 1 (Scheme 2a) had signals in the following regions: 6.12-6.14 ppm (d, H1, J=
6 Hz), 6.45-6.46 ppm (d, H2, 5.7 Hz), 6.54-6.56 ppm (dd, H4, J = 8.56 and 3,5 Hz), 6.69-6.71 (dd,
H3, J = 8.56 and 3,5 Hz) and 8.92 (s, 2H - which referred to the amide NH) . Bisamide 2 (Scheme
2b) had chemical shifts at 3.43 (m, H1), 7.66-7.68 (d, H3, J=8.56 Hz), 7.77-7.79 (d, H2, J=8.56 Hz)
and 8.67 ppm (s, 2H - which referred to the amide NH) (spectra can be found in the supplementary
material). Results of both compounds are consistent with the ones of similar compounds found in
the literature. [21]
Scheme 2: (a) Bisamide 1 with numbering in hydrogen atoms. (b) Bisamide 2 with numbering in
hydrogen atoms.
5

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Structures were confirmed by the XRD analysis. Both compounds had a monoclinic
crystalline system. Bisamide 1 belongs to the space group P 21/n, with final disagreement rates for
the following data: I > 2σ(I) R1 = 0.0374 and wR2 = 0.1082, R1 = 0.0850 and wR2 = 0.1357,
according to data collected by the analysis of 4067 independent reflections which were obtained by
the refinement of 29434 total reflections (Figure 1 and Table 2).
Figure 1: Structural representation of the asymmetric unit of Bisamide 1
Table 2. Data on intensity collection and refinement of crystalline/molecular structure of
Bisamide 1
Empirical formula
Molecular weight
Name
C20 H14 Br2 N2 O2
474,15 g/mol
1,2-bis(4-bromobenzamide)benzene
296 K
Temperature
0,71073 Å
Monoclinic
P 21/n
Wavelength/radiation
Crystal system
Space group
a = 9,6534(5) Å
Dimensions of unit cell
α= 90°
b = 19,7768(12) Å
c = 9,8465(5) Å
β= 99,607(2)°
γ = 90°
3
Volume
1853.46(18) Å
4
Z
3
Calculated density
1,699 Mg/m
-1
Absorption coefficient
4,390 mm
6

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936
F (000)
Dimensions of the glass
Angular region of scanning for data
collection
2,06 to 28,31°.
-12<=h<=12, -24<=k<=25, -9<=l<=12
29434
4067[R(int) = 0,0429]
Region of indices
Collected reflections
Independent reflections
99,.9 %
Completeness to θ= 25.24
Matrix of total least squares, including F2
R1 = 0,0374, wR2 = 0,1082
R1 = 0,0850, wR2 = 0,1357
Refinement method
Final indices of discordance I> 2σ (I)
Indices of discordance of all reflections
Residual electronic density (max and min)
-3
0,619 and -0,673 and Å
In Bisamide 1, attachment distances (tables in the supplementary material) C(17)-O(1)
correspond to a Csp2 = O double bond at 1.233 Å. Phenyl ring with bonding lengths are at 1.369 and
1.390 Å. The N(1) -C(21) bond is 1.353 Å long; these values are similar to those found in the
literature [25,26]. For C(14) -Br(1) bonding, the single bond length between C-Br is 1.898 Å.
In the case of Bisamide 1, lengths of the axes which define the unit cell of the monoclinic
system are, respectively, a= 9,654 (5) Å, b = 19.7768 (12) Å and 9.8465 (5) Å, perpendicular,
resulting in a unit cell with four units (Figure 2) [25,26].
7

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Figure 2: Projection of the structure of Bisamide 1 in the elemental cell
Bisamide 2 belongs to the space group P 21/c, with final disagreement rates for the
following data: I > 2σ(I) R1 = 0.0336 and wR2 = 0.0824, R1 = 0.0459 and wR2 = 0.0871, according
to data collected by the analysis of 1669 independent reflections which were obtained by the
refinement of 9726 total reflections (Figure 3 and Table 3).
8

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Figure 3: Structural representation of the asymmetric unit of Bisamide 2
Table 3: Data on intensity collection and refinement of crystalline/molecular structure of
Bisamide 2
Empirical formula
Molecular weight
Name
C16H14Br2N2O2
426,11 g/mol
,1,2-Bis (4-bromobenzamide)ethane
100 K
Temperature
0,56086 Å
Monoclinic
P 21/c
Wavelength/radiation
Crystal system
Space group
a = 8,4725(7)Å
b = 9,3594(7)Å
c = 9,8577(8)Å
= 90°
Dimensions of unit cell
= 95,127(2)°
= 90°
3
Volume
1853.46(18) Å
2
Z
3
Calculated density
1,818 Mg/m
-1
Absorption coefficient
2,797 mm
420
F (000)
0,33 x 0,22 x 0,18 mm
Dimensions of the glass
9

2.37 to 20.87°
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Angular region of scanning for data
collection
-10<=h<=10, -11<=k<=11, -12<=l<=12
Region of indices
9726
reflections Collected
Independent reflections
Completeness to θ= 25.24
Refinement method
1669 [R(int) = 0,0475]
99,9 %
Matrix of total least squares, including F2
R1 = 0,0336, wR2 = 0,0824
Final indices of discordance I> 2σ (I)
Indices of discordance of all reflections
Residual electronic density (max and min)
R1 = 0,0459, wR2 = 0,0871
-3
0,064 and -0,427 and.Å
In the case of Compound 2, the bond length between NC (2) and C (2) -O was, respectively,
1333 Å and 1238 Å. Bond length for C (1) -C (1 °) for the methylene groups was 1.528 Å.
Attachment lengths of the aromatic ring carbons were 1.379 and 1.385. C (6) -Br binding the single
bond length is 1,902Å. These values are consistent with a similar bisamide derivative, but they did
not agree with data found in the literature [25,26].
Regarding Bisamide 2, the length of the axes defining the unit cell of the monoclinic system
are, respectively, a = 8,4725(7) Å, b = 9,3594(7) Å e c = 9,8577(8) Å, perpendicular, resulting in a
unit cell with four units (Figure 4).
10

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Figure 4: Projection of the structure of Bisamide 2 in the elemental cell
These bisamides have different space structure. Bisamide 2 has an ethane group between the
nitrogen atoms of the amide moiety whereas Bisamide 1 has a more rigid structure among the
nitrogen atoms. These compounds were tested as auxiliary ligands of palladium in the Suzuki cross
coupling. The objective was to evaluate the influence of the separating group on the Suzuki reaction
and to deepen the study of this class of binders in the catalysis.
11

In the initial tests, coupling between phenylboronic acid and 4-bromotoluene was used.
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Firstly, different bases (K2CO3, Na2CO3 and EtONa), solvents (MeOH, EtOH, EtOH:H2O (1:1),
H2O, MeOH:H2O (1:1), DMF), reaction time (0.5, 1, 2, 4 and 8h) and temperature (70, 100 and 130
°C) were used. These reactions were followed by gas chromatographic analysis with internal
standard (undecane). Reaction tests showed excellent results at 70 °C with K2CO3 as the basis and
ethanol/water (1:1) as the solvent. Different sources of palladium were evaluated with both
synthesized bisamides. Besides, for this Pd-ligand system, the reaction time was also evaluated
(Table 4).
Table 4: Bisamide effect, source of palladium and time
[Pd], bisamide 1 or 2
base, solvent
ºC, time
+
Br
B(OH)2
Entry
Bisamide
[Pd]
(h)
Conv. (%)
Yield (%)
1
PdCl2
Pd(OAc)2
Pd(Acac)2
PdCl2
4
99
95
1
1
1
1
1
1
1
1
2
3
4
4
2
2
2
2
4
62
57
100
62
50
85
0
61
55
96
60
45
80
0
4
5
Pd(OAc)2
Pd(Acac)2
PdCl2
6
7a
8
------
12

9
PdCl
4
98
54
43
98
53
41
60
0
86
52
42
95
49
39
58
0
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2
2
10
Pd(OAc)2
Pd(Acac)2
PdCl2
4
4
2
2
2
2
4
2
2
11
2
12
13
2
Pd(OAc)2
Pd(Acac)2
PdCl2
2
14
15a
16
2
2
------
2
17
PdCl2
66
63
-------
Condition: aryl halides (1.0 mmol), arylboronic acid (1.5 mmol), K2CO3 (2 mmol), [Pd] (0.01
mmol), ligand (0.03 mmol), EtOH/H2O (6 mL, 1:1), 70ºC. a [Pd] (0.005 mmol)
Table 4 shows that the catalytic activity is mainly related to the palladium source. However,
the presence of bisamide as an auxiliary ligand is important because it facilitates its coordination to
the metal, making the oxidative addition step more efficient [3,27,28]. Test 16 shows that the
reaction does not occur without the palladium source whereas Test 17 shows that the reaction shows
low conversion and yields without an auxiliary binder.
After establishing that palladium chloride was the best catalytic source, the required
amounts of catalyst precursor and binder were analyzed (0.5, 1, 1.1 and 1.5 mol). Results obtained
by chromatographic analysis showed that, to enable the reaction under study to occur with total
conversion, 1 mol% PdCl2 and 1.1 mol ligand were needed.
13

The last stage of this study was to test different substrates (Table 5) in order to evaluate the
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effect of substituents.
Table 5: Results of the study of different substrates
PdCl2, bisamide 1 or 2
K2CO3, EtOH:H2O (1:1)
70 ºC, 2 h
+
Br
B(OH)2
R2
R1
R1
R2
Entry
R1
R2
H
Conv. (%)
Yield (%)
18
19
20
21
22
23*
4-NO2
99
99
99
98
99
55
95
94
97
97
96
53
4-CN
4-OCH3
CH3
H
H
4-CH3
4-OCH3
H
CH3
CH3
Condition: aryl halides (1.0 mmol), arylboronic acid (1.5 mmol), K2CO3 (2 mmol), PdCl2 (0.01
mmol), ligand (0.03 mmol), EtOH/H2O (6 mL, 1:1), 70ºC, 2 h.* 4-chlorotolueno.
This study showed excellent results of the Suzuki coupling for aryl bromides and aryl
boronic acid with either activating or deactivating substituents in the ring with high yield (entry 18-
22). Results of both bisamides were similar, an evidence of the fact that the source of palladium is
determinant in the reaction. This bisamide-palladium system was evaluated in the reaction between
chlorotoluene and phenylboronic acid. Even though results were modest, the one shown by entry
23 is promising, by comparison with other systems applied to aryl chlorides [29].
14

4 - CONCLUSION
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This study synthesized and characterized two different brominated bisamides and concluded
that they are excellent auxiliary ligands when coordinated to PdCl2. Bisamides were characterized
by different techniques, such as X-ray diffraction. After characterization, these compounds were
tested in the Suzuki reaction, in which good palladium auxiliary ligands were shown. It may be
concluded that, in the proposed system, it was fundamental to choose the source of palladium,
having PdCl2 as the best catalytic precursor. Besides, the separation group between nitrogen atoms
did not interfere in the catalytic result
Finally, the PdCl2-bisamide system was found to be quite efficient in reactions between aryl
bromides and arylboronic acids, both with aromatic and deactivating groups of the aromatic ring.
ACKNOWLEDGMENTS
We thank PRONEX FAPERGS/CNPq 307514/2013-7 for their financial support and CNPq for
granting a scholarship (D.P.C.) to Davi Back, Ph. D., who carried out the analysis of x-ray
1
diffraction. Integrated Analysis Center CIA-FURG, who carried out the analysis of H and 13C
NMR.
APPENDIX A. SUPPLEMENTARY DATA
Supplementary synthesis and data on NMR, IR and X-ray diffraction of bisamides and biphenlys
REFERENCES
[1] P. Jerome, P.N. Sathishkumar, N.S.P. Bhuvanesh, R. Karvembu, Towards phosphine-free Pd(II)
pincer complexes for catalyzing Suzuki-Miyaura cross-coupling reaction in aqueous medium, J.
Organometal Chem., 845 (2017), 115-124.
[2] M.K. Lakshman, Synthesis of biologically important nucleoside analogs by palladium-catalyzed
C-N bond-formation, Cur. Org Synt., 2 (2005), 83-112.
15

[3] A. Shen, Y.C. Hu, T.T. Liu, C. Ni, Y. Luo, Y.C. Cao, Supporting ligand-assisted N-heterocyclic
ACCEPTED MANUSCRIPT
carbene palladium complexes: characterization, computation, and catalytic activity in Suzuki-
Miyaura cross coupling between aryl and heteroaromatic chlorides and various boronic acids,
Tetrahedron Let., 57(2016), 2055-2058.
[4] M.M. Tamizh, K. Mereiter, K. Kirchner, R. Karvembu, Ruthenium(II) carbonyl complexes
containing 'pincer like' ONS donor Schiff base and triphenylphosphine as catalyst for selective
oxidation of alcohols at room temperature, J. Organom. Chem., 700 (2012), 194-201.
[5] M.A. Dufert, K.L. Billingsley, S.L. Buchwald, Suzuki-Miyaura Cross-Coupling of Unprotected,
Nitrogen-Rich Heterocycles: Substrate Scope and Mechanistic Investigation, J.Am.Chem.Soc., 135
(2013), 12877-12885.
[6] P. Paul, P. Sengupta, S. Bhattacharya, Palladium mediated C-H bond activation of
thiosemicarbazones: Catalytic application of organopalladium complexes in C-C and C-N coupling
reactions, J. Organom. Chem, 724 (2013), 281-288.
[7] A. Torrado, B. Iglesias, S. Lopez, A.R. Delera, The suzuki reaction in stereocontrolled polyene
synthesis - retinol (Vitamin-a), its 9-demethyl and/or 13-demethyl analogs, and related 9-demethyl-
dihydroretinoids, Tetrahedron, 51(1995), 2435-2454.
[8] Taylor P.N.; Connel, M.J.O.; McNeill L.A.; Hall M.J.;. Aplin R.T; Anderson H.L., Insulated
Molecular wires: Synthesis of conjugated polyrotaxanes by Suzuki coupling in water , Angew.
Chem.Int., 39 (2000), 3456-3460.
[9] N. Nomura, K. Tsurugi, N. Yoshida, M. Okada, Palladium-catalyzed allylic substitution reaction
in polymer synthesis, Cur. Org Synt., 2 (2005), 21-38.
[10] B.F. Mirjalili, M.A. Mirhoseini, Tandem synthesis of N,N '-alkylidenebisamides promoted by
nano-SnCl4 center dot SiO2, J. Chem.Sci., 125 (2013), 1481-1486.
[11] C. Ye, Z.Y. Chen, H.H. Wang, J. Wu, Generation of diverse 1-(isoquinolin-1-yl)guanidines via
a sequential multi-component/cross-coupling reaction, Tetrahedron, 68 (2012), 5197-5202.
16

[12] Y.-c. Li, Y.-j. Lin, S.-b. Zhang, S.-h. Li, H.-f. Duan, Aryl-guanidine/Pd-catalyzed Suzuki
ACCEPTED MANUSCRIPT
Cross-coupling Reaction at Room Temperature, Chem. Res. Chin. Univ., 28 (2012), 242-244.
[13] G.F. Chen, F. Wang, Y.H. Wang, X.C. Zhang, H.Q. Qin, H.F. Zou, J. Xu, Imine-linked
conjugated organic polymer bearing bis(imino)pyridine ligands and its catalytic application in C-C
coupling reactions, Chin. J. Cat., 35 (2014), 540-545.
[14] P. Lei, G.R. Meng, Y. Ling, J. An, M. Szostak, Pd-PEPPSI: Pd-NHC Precatalyst for Suzuki-
Miyaura Cross-Coupling Reactions of Amides, J. Org. Chem., 82 (2017), 6638-6646.
[15] S.H. Li, Y.J. Lin, J.G. Cao, S.B. Zhang, Guanidine/Pd(OAc)(2)-catalyzed room temperature
Suzuki cross-coupling reaction in aqueous media under aerobic conditions, J. Org. Chem., 72
(2007), 4067-4072.
[16] Banik B.; Tairai A.; Bhattacharyy P. K.; Das P., Excellent Suzuki–Miyaura catalytic activity
of a new Pd(II) complex with sulfonamide–Schiff base ligand, App. Organometal. Chem., 30
(2016), 519-523.
[17] S.M. Nobre, A.L. Monteiro, Pd complexes of iminophosphine ligands: A homogeneous
molecular catalyst for Suzuki-Miyaura cross-coupling reactions under mild conditions, J. Molec.
Cat. Chem., 313 (2009), 65-73.
[18] G.R. Meng, M. Szostak, Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-
nitrogen cleavage: general strategy for amide N-C bond activation, Org & Biomol.Chem., 14
(2016), 5690-5707.
[19] S.Y. Ni, W.Z. Zhang, H.B. Mei, J.L. Han, Y. Pan, Ni-Catalyzed Reductive Cross-Coupling of
Amides with Aryl Iodide Electrophiles via C-N Bond Activation, Org. Let., 19 (2017), 2536-2539.
[20] R.M. de Figueiredo, J.S. Suppo, J.M. Campagne, Nonclassical Routes for Amide Bond
Formation, Chem. Rev., 116 (2016), 12029-12122.
[21] D.P. da Costa, S.M. Nobre, Bisamides as ligands in Suzuki coupling reactions catalyzed by
palladium, Tetrahedron Let., 54 (2013), 4582-4584.
17

[22] H.Y. Liu, K. Wang, H.Y. Fu, M.L. Yuan, H. Chen, R.X. Li, Amide as an efficient ligand in the
ACCEPTED MANUSCRIPT
palladium-catalyzed Suzuki coupling reaction in water/ethanol under aerobic conditions, Chin.
Chem. Let., 22 (2011), 738-740.
[23] P.J. Cappillino, P.C. Tarves, G.T. Rowe, A.J. Lewis, M. Harvey, C. Rogge, A. Stassinopoulos,
W. Lo, W.H. Armstrong, J.P. Caradonna, Synthesis and characterization of a family of binuclear
non-heme iron monooxygenase model compounds: Evidence for a "phenolate/amide carbonyl
(PAC) shift" upon oxidation, Inorg. Chim. Acta., 362 (2009), 2136-2150.
[24] B. Saikia, P.R. Boruah, A.A. Ali, D. Sarma, Simple and efficient phosphine-free Pd(OAc)(2)
catalyzed urea accelerated Suzuki-Miyaura cross-coupling reactions in (PrOH)-Pr-i-H2O at room
temperature, Tetrahedron Let., 56 (2015), 633-635.
[25] N.L. Fry, M.J. Rose, D.L. Rogow, C. Nyitray, M. Kaur, P.K. Mascharak, Ruthenium Nitrosyls
Derived from Tetradentate Ligands Containing Carboxamido-N and Phenolato-O Donors:
Syntheses, Structures, Photolability, and Time Dependent Density Functional Theory Studies,
Inorg.Chem., 49 (2010), 1487-1495.
[26] D.P. da Costa, S.M. Nobre , B.G. Lisboa, J.R.d.M. Vicenti , D.F. Back 2,2′-Dihydroxy-N,N′-
(ethane-1,2-di-yl)di-benzamide, Acta Cristalograf- (E), , Section S (2013) UP 1.
[27] J.M. Neely, M.J. Bezdek, P.J. Chirik, Insight into Transmetalation Enables Cobalt-Catalyzed
Suzuki-Miyaura Cross Coupling, C. Sci., 2 (2016), 935-942.
[28] F.Y. Fu, J. Xiang, H. Cheng, L.J. Cheng, H.B. Chong, S.X. Wang, P. Li, S.Q. Wei, M.Z. Zhu,
Y.D. Li, A Robust and Efficient Pd-3 Cluster Catalyst for the Suzuki Reaction and Its Odd
Mechanism, Catalysis, 7(2017), 1860-1867.
[29] Q.Y. Deng, Y.J. Shen, H.B. Zhu, T. Tu, A magnetic nanoparticle-supported N-heterocyclic
carbene-palladacycle: an efficient and recyclable solid molecular catalyst for Suzuki-Miyaura cross-
coupling of 9-chloroacridine, Chem. Comm., 53 (2017), 13063-13066.
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ACCEPTED MANUSCRIPT
Scheme 1: Synthesis of 1,2-bis(4-bromobenzamide)benzene (Bisamide 1) and 1,2-bis (4-
bromobenzamide)ethane (Bisamide 2)
Scheme 2: (a) Bisamide 1 with numbering in hydrogen atoms. (b) Bisamide 2 with numbering in
hydrogen atoms
Figure 1: Structural representation of the asymmetric unit of Bisamide 1
Figure 2: Projection of the structure of Bisamide 1 in the elemental cell
Figure 3: Structural representation of the asymmetric unit of Bisamide 2
Figure 4: Projection of the structure of Bisamide 2 in the elemental cell
Table 1. Comparison among the main bands found in the literature
Table 2. Data on intensity collection and refinement of crystalline/molecular structure of
Bisamide 1
Table 3: Data on intensity collection and refinement of crystalline/molecular structure of
Bisamide 2
Table 4: Bisamide effect, source of palladium and time
Table 5: Results of the study of different substrates
19

ACCEPTED MANUSCRIPT
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Synthesis brominated bisamides,
Bisamides in Suzuki,
Choice of the best catalyst.