A convenient palladium catalyzed synthesis of symmetric biaryls, biheterocycles and biaryl chiral diamides

Article abstract of DOI:10.1016/j.tet.2005.02.019

A series of symmetrical diamido biaryls has been synthesized in good yield by direct homocoupling of iodoarylbenzamides by palladium-catalysis. No cross product has been isolated from the reaction mixture of two different iodoarylbenzamides under similar conditions. However, only in the case of 2-iodo-N-phenylbenzamide, the intramolecularly coupled product phenanthridone has been isolated as a minor product along with the major intermolecularly coupled product. Biphenyl chiral diamides have been synthesized by this coupling method. This coupling reaction also works well with the reductive dimerization of functionalized heterocyclic compounds. Thus 6,6′-dipivaloylamino-3, 3′-bipyridine and 6,6′-dimethyl-2,2′-bipyridine have been efficiently synthesized. In two cases, the X-ray crystal structures have been solved to establish the structures of symmetrical and chiral diamido biaryls and their supramolecular networks.

Full text of DOI:10.1016/j.tet.2005.02.019

Tetrahedron 61 (2005) 4289–4295
A convenient palladium catalyzed synthesis of symmetric biaryls,
biheterocycles and biaryl chiral diamides
a
a,†
Shyamaprosad Goswami,a, Avijit Kumar Adak, Reshmi Mukherjee, Subrata Jana,a
*
Swapan Deya and John F. Gallagherb,‡
aDepartment of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, West Bengal, India
bSchool of Chemical Sciences, Dublin City University, Dublin 9, Ireland
Received 26 October 2004; revised 24 January 2005; accepted 10 February 2005
Available online 17 March 2005
Abstract—A series of symmetrical diamido biaryls has been synthesized in good yield by direct homocoupling of iodoarylbenzamides by
palladium-catalysis. No cross product has been isolated from the reaction mixture of two different iodoarylbenzamides under similar
conditions. However, only in the case of 2-iodo-N-phenylbenzamide, the intramolecularly coupled product phenanthridone has been
isolated as a minor product along with the major intermolecularly coupled product. Biphenyl chiral diamides have been synthesized by this
coupling method. This coupling reaction also works well with the reductive dimerization of functionalized heterocyclic compounds. Thus
6,60-dipivaloylamino-3,30-bipyridine and 6,60-dimethyl-2,20-bipyridine have been efficiently synthesized. In two cases, the X-ray crystal
structures have been solved to establish the structures of symmetrical and chiral diamido biaryls and their supramolecular networks.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
We report here the results of our observation of palladium
catalyzed reaction of iodoarylbenzamides to prepare
symmetrical biaryl diamides, including biaryl chiral dia-
mides, by a modified procedure. During our investigation of
the palladium catalyzed homocoupling reaction of 1a by
using (Ph3P)2PdCl2 as a catalyst, we have unexpectedly
isolated an intramolecularly coupled product 2 (15–20%) as
a minor product (Scheme 1).
Highly functionalized symmetrical biaryl subunits are
present in a large number of natural products such as
tellimagrandins,1a (K) gossypol1b and are also used in
materials science as precursors to rigid liquid crystals1c as
well as semi conducting complexes, and consequently gain
much attention for their synthesis.1e There are various
coupling methods, and the application of these methods
have been recently reviewed.2 The most convenient method
for the synthesis of symmetrical biaryls is reductive
homocoupling of arylhalides either by Ullmann synthesis3
or by oxidative coupling of arylboronic acid,4a arylzinc,4b
arylstannanes4c and aryl mesylates.4d However, palladium
catalyzed coupling reactions are among the most important
C–C bond forming reactions in organic synthesis.5 Lemaire
et al.6 have synthesized functionalized symmetrical biaryls
and biheterocycles via the homocoupling of aryl halides
using Pd(OAc)2 in the presence of n-Bu4NBr and K2CO3.
However, palladium catalyzed reductive homocoupling of
aryl halides using ionic liquid7 and zinc powder-formate
salt8 are also known.
Scheme 1. (i) (Ph3P)2PdCl2, CuI, Et3N, DMF, 120 8C, 12 h.
The symmetrical diamido biaryls 3a–g was synthesized in
good yields from direct self-coupling of iodoarylbenz-
amides 1a–g along with the biaryl chiral diamides 5 and 6
by palladium catalyzed reactions. No cross product was
isolated from the reaction mixture of 1a and 1b under
similar conditions. Only in the case of 1a, did cyclization
leading to a phenanthridone 2 occur. The crystal structures
Keywords: Symmetric biaryls; Palladium catalyzed reaction; Homocou-
pling; Ullmann reaction; Biaryl chiral diamides.
*
Corresponding author. Tel.: C91 3326684561; fax: C91 3326682916;
e-mail: spgoswamical@yahoo.com
2
2
0
of 3a (N ,N -diphenyl [1,10-biphenyl]-2,20-dicarboxamide)
and 6 (biphenyl-2,20-dicarboxylic acid bis-[(1R-phenyl-
ethyl)-amide]) reveal the detailed structures of symmetrical
† Presently at the University of Zurich, Switzerland.
‡ Fax: C353 1 7005503.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.019

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S. Goswami et al. / Tetrahedron 61 (2005) 4289–4295
Table 1. Yield of products (3a–g) of palladium catalyzed coupling
reactions of 1a–g
and chiral diamido biaryls and their interesting supra-
molecular networks.
Entry
2-Iodo-N-arylbenzamides
(1a–g)
Symmetrical diamido-
biaryls (3a–g)
Yield
(%)
According to the reported procedure,9a it is necessary to
protect the N–H function of 1a with an alkyl group to obtain
the cyclized product 2 (N-protected) by a palladium
catalyzed dehydrohalogenation reaction since palladium
forms a cyclic complex between the halogen bearing carbon
and the N–H function. However, the N-butyryl protected
derivative of 2-iodo-N-phenyl-benzamide 1a formed the
intermolecularly coupled product 3a in the Heck reaction9b
using tri-o-tolylphosphine, palladium acetate and sodium
carbonate in DMF under reflux for one and a half hours
where selective deprotection of the N-butyryl group
occurred (Scheme 2).
1.
2.
3.
4.
5.
6.
7.
1a: XZCH, RZH
3a: XZCH, RZH
70
66
70
68
1b: XZCH, RZ2-Me
1c: XZCH, RZ3-Me
1d: XZCH, RZ4-OMe
1e: XZCH, RZ4-CO2Et 3e: XZCH, RZ4-CO2Et 56
1f: XZN, RZH
3b: XZCH, RZ2-Me
3c: XZCH, RZ3-Me
3d: XZCH, RZ4-OMe
3f: XZN, RZH
3g: XZN, RZ6-Me
54
65
1g: XZN, RZ6-Me
The results of the palladium catalyzed homocoupling
reactions of various iodoarylbenzamides are shown in
Table 1.
We have prepared the biphenyl chiral diamides 5 and 6 from
7 and 8, respectively, (Scheme 4). Protection of the
hydroxyl group in R(K)-2-amino-1-butanol was not
necessary as evident by the following observation. Reaction
of R(K)-2-amino-1-butanol with 2-iodobenzoyl chloride
afforded the chiral 2-iodobenzamide 7. Subsequent coupling
of 7 gave the biphenyl chiral diamide 5 as a brown-semi
solid in 54% yield using similar conditions as before.
Scheme 2. (i) Butyryl chloride, Et3N, dry C6H6, reflux, 24 h; (ii) Pd(OAc)2,
(o-tol)3P, Na2CO3, DMF, reflux, 1.5 h.
Intramolecular palladium catalyzed reactions are well
established in the synthesis of benzo[c]phenanthridine or
fully aromatized phenanthridine alkaloids.9b–e Interestingly
when 1a was subjected to Pd(PPh3)2Cl2 catalyzed coupling
reaction, the major product was the intermolecularly
coupled diphenyl diamide 3a along with the minor
intramolecularly coupled product phenanthridinone 2.
Then 1a was subjected to a reaction using Pd(OAc)2 as
the catalyst with Ph3P and Et3N, and no intramolecularly
coupled product 2 was obtained but the only isolated
product was the biaryl, 3a. This homocoupling reaction was
then performed with a series of 2-iodo-N-arylbenzamides
1a–e using a variety of catalysts and solvents, for example,
Pd(Ph3P)2Cl2/CuI, Pd(OAc)2/Ph3P/CuI, Pd(OAc)2/
(o-tolyl)3P/CuI in DMF or acetonitrile and with a base,
Et3N. However, the best conditions were to use a catalytic
amount of Pd(OAc)2/Ph3P/CuI and Et3N in refluxing
acetonitrile. This catalyst system was also examined with
heterocyclic compounds, for example, 2-iodo-N-pyridin-2-
ylbenzamides 1f–g. In all these cases, 2-iodo-N-arylbenz-
amides 1a–g (obtained from the corresponding amines 4a–g)
underwent conversion only to biaryls 3a–g in good yields
showing the generality of this method for the intermolecular
biaryl coupling reactions (Scheme 3).
Scheme 4. (i) 2-Iodobenzoyl chloride, dry CH2Cl2, Et3N, rt, 6 h;
(ii) Pd(OAc)2, Ph3P, CuI, Et3N, CH3CN, reflux, 6–8 h.
Similarly, R(C)-a-methylbenzylamine was converted to
the iodobenzamide 8 which on palladium catalyzed
coupling reaction afforded the biphenyl chiral diamide 6
as a white crystalline solid in 70% yield.
The coupling reaction using these conditions was also
found to be successful with the synthesis of homocoupled
bi-heterocyclic compounds. These compounds are useful
for molecular recognition research and in metal directed
assembly and also in the synthesis of metal helicates.10
Thus 3,30- and 2,20- coupled functionalized bipyridyl
compounds 9 and 10 were synthesized efficiently by
this method (Scheme 5). For the 3,30-coupling reaction,
2-N-pivaloyl-3-bromopyridine required 12 h at reflux in
comparison to the chloro analog, which required 46 h.
1
All of the biaryls were characterized by H NMR and also
by mass spectrometric studies. Single crystal X-ray
diffraction11 studies in two cases (achiral 3a and chiral 6)
confirmed their biphenyl structures.
Scheme 3. (i) 2-Iodobenzoyl chloride (1.1 equiv), dry CH2Cl2, Et3N, rt;
(ii) Pd(OAc)2, PPh3, CuI, Et3N, acetonitrile, reflux, 6–8 h.

S. Goswami et al. / Tetrahedron 61 (2005) 4289–4295
4291
molecular hydrogen bonding amide/amide systems as
N-H/O]C hydrogen bonds with graph-set C(4).12
However, the intermolecular hydrogen bonding in 3a
displays a six-membered hydrogen bonding motif involving
the adjacent amido NH and phenyl CH moieties interacting
with the amide oxygen of a symmetry related molecule.
This motif is absent in the chiral analogue 6 (Fig. 2), which
only shows the normal N–H/O]C type hydrogen
˚
bonding, N/O 2.912(3) A, N–H/O 1638. This is perhaps
due to the extra rigidity of the geometry in 6 together with
the presence of a chiral centre between the amide NH and
the phenyl group.
Scheme 5. (i) Pd(OAc)2, Ph3P, CuI, Et3N, CH3CN, reflux, 12–40 h.
As depicted in Figure 1, the biaryl 3a is biphenyl-2,20-
dicarboxylic acid 20-amide 2-phenylamide. Interestingly,
the supramolecular structure of the biphenyl diamide shows
that one amide oxygen accepts two intermolecular hydrogen
In both the biphenyl diamides (achiral 3a and chiral 6),
the biphenyl rings are shown close to be perpendicular by
the presence of only one amide group at the a position
to each ring. The central rings are at angles 78.98 for 3a
(in tetragonal system) and 78.388 (in orthorhombic system).
bonds {N–H and C–H from another molecule, graph set
1
˚
˚
C(4), R2(6), N/O 2.857(6) A and C/O 3.313(8) A with
N–H/O/C–H/O 165 and 1378, respectively} together
with the trans amide NH which forms one intramolecular
hydrogen bond with amide oxygen, set S(9), N/O
3. Conclusion
˚
˚
2.857(6) A N/O 2.919(6) A. These geometric values
have similar dimensions to those found in related inter-
We thus present here an efficient method for the preparation
Figure 1. X-ray crystal structure of 3a (above left) together with a view of the interactions (above right).
Figure 2. X-ray crystal structure of 6 (above left) together with a view of the interactions (above right).

4292
S. Goswami et al. / Tetrahedron 61 (2005) 4289–4295
of symmetrical diamido biaryls by palladium catalyzed
homocoupling reaction as well as for the preparation of
biphenyl chiral amides. The advantage is that we get the
reductive coupling instead of dehalogenative coupling or
simple reduction products, even though we have used
palladium salt in the presence of Et3N in an aprotic solvent
like CH3CN or DMF. The coupling reaction also works
well in the synthesis of biheterocycles, for example, func-
tionalized bipyridyls depending on the position of halogens.
The crystal structures of achiral 3a and chiral 6 were solved
to confirm their structures along with exploring the amide–
amide hydro0gen bond induced supramolecular network in
biphenyl 1,1 -diamides. We are currently investigating the
application of this methodology in the synthesis of biphenyl
or biheterocyclic designed molecules containing suitable
amide substrates for studies in molecular recognition and
supramolecular chemistry.
7.70–7.39 (m, 6H), 7.25–7.17 (m, 2H), 6.60 (br. S, 1H, NH,
D2O exchangeable).
4.1.2. 2-Iodo-N-o-tolyl-benzamide (1b).14 Yield: (96%);
white crystalline solid; mp 195–197 8C. FT-IR (KBr): 3342,
1
1649, 1523, 1456, 1310, 1016, 753, 669 cmK1. H NMR
(CDCl3, 300 MHz): d (ppm)Z8.01 (d, 1H, JZ7.9 Hz), 7.92
(d, 1H, JZ7.8 Hz), 7.55 (d, 1H, JZ7.2 Hz), 7.45 (t, 1H, JZ
7.3 Hz), 7.31–7.22 (m, 2H), 7.25 (br s, 1H, NH), 7.19–7.11
(m, 2H), 2.36 (s, 3H).
4.1.3. 2-Iodo-N-m-tolyl-benzamide (1c).14 Yield: (95%);
white solid; mp 155–157 8C. FT-IR (KBr): 3243, 1652,
1541, 1316, 779, 740 cmK1. 1H NMR (CDCl3, 300 MHz): d
(ppm)Z7.92 (d, 1H, JZ7.9 Hz), 7.51 (s, 1H), 7.46–7.41 (m,
3H), 7.38 (br s, 1H, NH), 7.29–7.24 (m, 1H), 7.15 (t, 1H, JZ
7.6 Hz), 6.99 (d, 1H, JZ7.4 Hz), 2.39 (s, 3H).
4.1.4. 2-Iodo-N-(4-methoxy-phenyl)-benzamide (1d).14
Yield: (95%); white solid; mp 155–157 8C. FT-IR (KBr):
4. Experimental
3308, 1651, 1513, 825, 741 cmK1 1H NMR (CDCl3,
.
All the reactions were carried out under nitrogen atmos-
phere in anhydrous solvents. CH2Cl2, DMF and Et3N were
distilled over CaH2 and CH3CN over P2O5. All chromato-
graphic separations were performed on silica gel (100–200
mesh). For preparative thin layer chromatographic (PTLC)
purification, the layer was formed on a glass plate using
water gel-GF 254 silica gel. The petroleum ether used has a
boiling range of 40–60 8C. Mps were uncorrected. 1H NMR
spectra were recorded either on a Bruker AM 300L MHz
or a Bruker 500 MHz spectrometer. 13C NMR spectra were
recorded on a Bruker 500 MHz spectrometer. For NMR
spectra, CDCl3 was used as solvent unless otherwise
mentioned using TMS as internal standard. Chemical shifts
are expressed in d unit and 1H–1H, 1H–C coupling constants
in Hz. IR spectra were recorded on a Perkin–Elmer
Spectrum I spectrophotometer using KBr discs. Optical
rotations are measured in a JASCO DIP 360 polarimeter.
Mass spectra (JEOL JMS600) were obtained from the
Indian Institute of Chemical Biology, Kolkata and the
Philipps-Universitat, Marburg, Germany.
300 MHz): d (ppm)Z7.90 (d, 1H, JZ7.8 Hz), 7.57–7.50
(m, 3H), 7.42 (t, 1H, JZ7.3 Hz), 7.37 (br s, 1H, NH), 7.14
(t, 1H, JZ7.6 Hz), 6.92 (d, 2HH, JZ8.9 Hz), 3.81 (s, 3H).
4.1.5. 4-(2-Iodo-benzoylamino)-benzoic acid ethyl ester
(1e). Yield: (90%); cream colored solid; mp 110–112 8C.
FT-IR (KBr): 3331, 1701, 1664, 1598, 1533, 1405, 1281,
1174, 1017, 769, 752, cmK1. 1H NMR (CDCl3, 300 MHz):
d (ppm)Z8.07 (d, 1H, JZ8.6 Hz), 7.93 (d, 1H, JZ7.7 Hz),
7.85 (d, 1H, JZ8.6 Hz), 7.72 (d, 1H, JZ8.4 Hz), 7.65 (br s,
1H, NH), 7.54 (d, 1H, JZ8.5 Hz), 7.45 (d, 1H, JZ7.4 Hz),
7.17 (t, 1H, JZ7.5 Hz), 6.64 (d, 1H, JZ6.9 Hz), 4.37 (q,
2H, JZ7.1 Hz), 1.40 (t, 3H, JZ7.1 Hz). Anal. Calcd for
C16H14NO3I: C, 48.62; H, 3.57; N, 3.54. Found: C, 48.60;
H, 3.60; N, 3.58.
4.1.6. 2-Iodo-N-pyridin-2-yl-benzamide (1f). Yield:
(88%); cream colored solid; mp 92–94 8C. FT-IR (KBr):
1
2977, 1681, 1579, 1433, 1309, 1015, 780 cmK1. H NMR
(CDCl3, 300 MHz): d (ppm)Z10.15 (br s, 1H, NH), 8.52 (d,
1H, JZ8.4 Hz), 8.23 (d, 1H, JZ6.8 Hz), 8.00 (d, 1H, JZ
8.1 Hz), 7.94 (t, 1H, JZ7.0 Hz), 7.88 (t, 1H, JZ7.6 Hz),
7.61 (d, 1H, JZ7.8 Hz), 7.48–7.38 (m, 1H), 7.15 (t, 1H, JZ
6.5 Hz).
4.1. General procedure for the preparation of 2-iodo-N-
arylbenzamides
To a magnetically stirred solution of the amines (1.0 mmol)
in dry CH2Cl2 (20 ml) and freshly distilled Et3N (1.2 equiv),
was added 2-iodobenzoyl chloride (1.1 equiv), and stirring
was continued for 6–12 h. The triethylamine hydrochloride
was filtered off, and the organic layer after washing with
water was dried (anhydrous Na2SO4) and then the solvent
was removed under reduced pressure. The residue was
purified using silica-gel chromatography to afford the
corresponding 2-iodo-N-arylbenzamides (1a–g), 7 and 8 in
almost quantitative yields.
4.1.7. 2-Iodo-N-(6-methyl-pyridin-2-yl)-benzamide (1g).
Yield: (92%); white crystalline solid; mp 101–103 8C.
FT-IR (KBr): 3240, 2983, 1683, 1576, 1454, 1136, 1016,
1
798, 749 cmK1. H NMR (CDCl3, 300 MHz): d (ppm)Z
8.35 (br s, 1H, NH), 8.17 (d, 1H, JZ8.1 Hz), 7.91 (d, 1H,
JZ8.0 Hz), 7.66 (t, 1H, JZ7.8 Hz), 7.49 (d, 1H, JZ
7.5 Hz), 7.40 (t, 1H, JZ7.5 Hz), 7.14 (t, 1H, JZ7.7 Hz),
6.93 (d, 1H, JZ7.5 Hz), 2.45 (s, 3H). Anal. Calcd for
C13H11N2OI: C, 46.17; H, 3.27; N, 8.28. Found: C, 46.15;
H, 3.30; N, 8.30.
Representative data for iodoarylbenzamides were as
follows.
4.1.8. N-(1R-Hydroxymethyl-propyl)-2-iodo-benzamide
(7). Yield: (94%); off-white solid; mp 106–108 8C. FT-IR
(KBr): 3264, 2962, 1644, 1540, 1042, 725 cmK1. 1H NMR
(CDCl3, 300 MHz): d (ppm)Z7.77 (d, 1H, JZ7.8 Hz),
7.35–7.27 (m, 2H), 7.05–6.99 (m, 1H), 5.90 (d, 1H, JZ
7.8 Hz, NH), 4.03–3.98 (m, 1H), 3.77 (dd, 1H, JZ3.5,
4.1.1. 2-Iodo-N-phenyl-benzamide (1a). Yield: (98%); off-
white powder; mp 140–142 8C [lit.13 143–145 8C]. FT-IR
(KBr): 3446, 2360, 1698, 1299, 696 cmK1 1H NMR
.
(CDCl3, 200 MHz): d (ppm)Z7.97 (d, 1H, JZ7.8 Hz),

S. Goswami et al. / Tetrahedron 61 (2005) 4289–4295
4293
3.5 Hz), 3.65 (dd, 1H, JZ5.1, 5.1 Hz), 2.40 (br s, 1H, OH),
1.71–1.51 (m, 2H), 0.98 (t, 3H, JZ7.4 Hz). Anal. Calcd for
C11H14NO2I: C, 41.39; H, 4.42; N, 4.38. Found: C, 41.35;
H, 4.45; N, 4.40.
(Na2SO4). Removal of solvent followed by column
chromatography afforded the white crystalline solid 3a
(25 mg, 70%) identical in all respects with the material
described above. This protocol was successfully applied for
other iodoarylbenzamides 1b–g and for chiral 7 and 8.
4.1.9. N-(1R-Phenyl-ethyl)-2-iodo-benzamide (8). Yield:
(96%); off-white solid; mp 85–87 8C. FT-IR (KBr): 3299,
4.3.1. N-Butyryl-2-iodo-N-phenyl-benzamide (1a0). A
mixture of 2-iodo-N-phenyl-benzamide 1a (324 mg,
1 mmol), butyryl chloride (0.114 ml, 1.1 mmol) and Et3N
(0.153 ml, 1.1 mmol) in dry benzene was refluxed for 24 h
under N2 atmosphere. The product was purified by silica gel
chromatography [CH2Cl2 and pet-ether (1:1)] to afford the
butyryl protected derivative 1a0 as a cream-colored semi
solid.
1
1640, 1529, 1447, 1317, 1014, 873, 743, 698 cmK1. H
NMR (CDCl3, 300 MHz): d (ppm)Z7.84 (d, 1H, JZ
7.8 Hz), 7.44–7.25 (m, 7H), 7.10–7.05 (m, 1H), 6.00 (br s,
1H, NH), 5.34 (p, 1H, JZ7.3 Hz), 1.64 (d, 3H, JZ6.9 Hz).
Anal. Calcd for C15H14NOI: C, 51.29; H, 4.01; N, 3.98.
Found: C, 51.26; H, 4.10; N, 4.00.
4.2. 5H-Phenanthridin-6-one (2) and biphenyl-2,20-
dicarboxylic acid bis-phenylamide (3a)
FT-IR (KBr): 3446, 2360, 1698, 1299, 696 cmK1. 1H NMR
(CDCl3, 300 MHz): d (ppm)Z7.68 (d, 1H, JZ8.1 Hz),
7.34–7.17 (m, 7H), 6.95 (m, 1H), 2.51 (t, 2H, JZ5.6 Hz),
1.65–1.52 (m, 2H), 0.84 (t, 3H, JZ7.4 Hz). Anal. Calcd for
C17H16NO2I: C, 51.91; H, 4.10; N, 3.56. Found: C, 51.90;
H, 4.12; N, 3.60.
In a typical reaction procedure, a mixture of 2-iodo-N-
phenyl-benzamide 1a (340 mg, 1.05 mmol), Pd(PPh3)2Cl2
(12 mg, 0.015 mmol), CuI (2.85 mg, 0.015 mmol), Et3N
(0.5 ml) and dry DMF (5.0 ml) was stirred at 120 8C for 12 h
under nitrogen atmosphere. DMF was then distilled off,
methylene chloride was then added and filtered through a
pad of celite (3–4 cm). The organic layer was washed well
with water followed by brine and then dried (Na2SO4).
Removal of solvent followed by column chromatography
furnished white solid 2 (30 mg, 15%) followed by 3a
(60 mg, 58%) as white crystalline solid.
4.4. Palladium catalyzed coupling of butyryl protected
derivative (1a0)
A mixture of butyryl protected derivative 1a0 (100 mg,
0.264 mmol), Pd(OAc)2 (2.97 mg, 0.0132 mmol), (o-tol)3P
(4.02 mg, 0.0132 mmol) and Na2CO3 (23.34 mg) in dry
DMF (5.0 ml) was stirred at 150 8C for 1.5 h under nitrogen
atmosphere. The reaction mixture was then evaporated to
dryness, CH2Cl2 was added and filtered through a pad of
celite (3–4 cm). After usual work-up and purifications, 3a
was isolated as a white crystalline solid (31 mg, 60%)
identical in all respects with the above.
1
4.2.1. 5H-Phenanthridin-6-one (2). Mp 198 8C. H NMR
(CDCl3, 200 MHz): d (ppm)Z9.46 (bs, 1H), 7.75–7.08 (m,
8H). 13C NMR (CDCl3, 125 MHz): dZ169.5, 138.16,
132.27, 132.07, 130.19, 129.80, 128.93, 128.74, 128.50,
128.15, 127.38, 124.47, 120.09. MS (EI): m/z (%)Z195.1
(MC, 14%), 122.1 (70%), 106.1 (100%). Anal. Calcd for
C13H9NO: C, 79.98; H, 4.65; N, 7.17. Found: C, 79.96; H,
4.64; N, 7.15.
4.4.1. Biphenyl-2,20-dicarboxylic acid bis-o-tolylamide
(3b). Cream colored solid; mp 230–232 8C [lit.16 236 8C].
UV/vis (CHCl3): lmax (log 3)Z247 nm (8.4). FT-IR (KBr):
1
3434, 2922, 1644, 1527, 1458, 1317, 1059, 757 cmK1. H
4.2.2. Biphenyl-2,20-dicarboxylic acid bis-phenylamide
(3a). Mp 228–229 8C [lit.15 229–230 8C]. UV/vis (CHCl3):
lmax (log 3)Z258 nm (8.7). FT-IR (KBr): 3444, 3251, 1644,
1540, 1488, 1321, 776 cmK1. 1H NMR (CDCl3, 500 MHz):
d (ppm)Z8.81 (bs, 2H), 7.26 (d, 2H, JZ8.6 Hz), 7.36–7.31
(m, 8H), 7.19 (t, 4H, JZ7.8 Hz), 7.12 (d, 2H, JZ8.5 Hz),
7.00 (t, 2H, JZ7.3 Hz). 13C NMR (CDCl3, 125 MHz): d
(ppm)Z168.75, 139.51, 138.35, 136.53, 130.58, 130.13,
129.30, 128.52, 127.62, 124.88, 120.40. MS (EI): m/z (%)Z
392.1 (MC, 34%), 271.9 (31%), 181 (100%), 28 (75%).
Anal. Calcd for C26H20N2O2: C, 79.59; H, 5.10; N, 7.14.
Found: C, 79.55; H, 5.14; N, 7.23.
NMR (CDCl3, 500 MHz): d (ppm)Z8.35 (bs, 2H), 6.63 (d,
2H, JZ8.8 Hz), 7.40–7.37 (m, 4H), 7.34 (d, 2H, JZ7.9 Hz),
7.22 (d, 2H, JZ8.7 Hz), 7.04 (t, 4H, JZ6.5 Hz), 6.98 (t, 2H,
JZ7.0 Hz), 1.99 (s, 6H). MS (EI): m/z (%)Z420 (MC,
30%), 286 (25%), 181 (100%), 91 (28%). Anal. Calcd for
C28H24N2O2: C, 79.98; H, 5.75; N, 6.66. Found: C, 80.00;
H, 5.74; N, 6.70.
4.4.2. Biphenyl-2,20-dicarboxylic acid bis-m-tolylamide
(3c). White crystalline solid; mp 208–210 8C. UV/vis
(CHCl3): lmax (log 3)Z256 nm (10.7). FT-IR (KBr):
3443, 3264, 2925, 1645, 1598, 1550, 1440, 1331,
1
755 cmK1. H NMR (CDCl3, 500 MHz): d (ppm)Z8.68
4.3. Synthesis of biphenyl-2,20-dicarboxylic acid bis-
phenylamide (3a). A general representative reaction
procedure for symmetrical biaryls
(bs, 2H), 7.62 (d, 2H, JZ8.5 Hz), 7.36–7.31 (m, 4H), 7.24
(s, 2H), 7.13 (d, 2H, JZ8.5 Hz), 7.10–7.05 (m, 4H), 6.82 (d,
2H, JZ6.9 Hz), 2.24 (s, 6H). 13C NMR (CDCl3, 125 MHz):
d (ppm)Z168.70, 139.52, 139.22, 138.29, 136.62, 130.53,
130.12, 129.08, 128.48, 127.63, 125.69, 121.03, 117.54,
21.87. MS (EI): m/z (%)Z420.4 (MC, 40%), 286.2 (35%),
181 (100%), 116 (41%). Anal. Calcd for C28H24N2O2: C,
79.98; H, 5.75; N, 6.66. Found: C, 79.95; H, 5.76; N, 6.68.
A mixture of 2-iodo-N-phenyl-benzamide 1a (120 mg,
0.37 mmol), Pd(OAc)2 (3.36 mg, 0.015 mmol), CuI
(2.85 mg, 0.015 mmol), Ph3P (10 mg, 0.03 mmol), Et3N
(0.25 ml) and CH3CN (5.0 ml) was stirred at 82 8C for 6 h
under nitrogen atmosphere. The reaction mixture was then
evaporated to dryness, CH2Cl2 was added and filtered
through a pad of celite (3–4 cm). The organic layer was
washed well with water followed by brine and then dried
4.4.3. Biphenyl-2,20-dicarboxylic acid bis-[(4-methoxy-
phenyl)-amide] (3d). White solid; mp 120–122 8C. UV/vis

4294
S. Goswami et al. / Tetrahedron 61 (2005) 4289–4295
(CHCl3): lmax (log 3)Z239 nm (10.1). FT-IR (KBr): 3307,
2955, 1650, 1512, 1232, 824, 741 cmK1. 1H NMR (CDCl3,
500 MHz): d (ppm)Z8.82 (bs, 2H), 7.60 (d, 2H, JZ8.6 Hz),
7.32–7.30 (m, 4H), 7.22 (d, 4H, JZ6.9 Hz), 7.10 (d, 2H, JZ
6.4 Hz), 6.71 (d, 4H, JZ6.9 Hz), 3.67 (s, 6H). MS (EI): m/z
(%)Z452.0 (MC, 40%), 330 (30%), 181 (100%), 123
(85%). Anal. Calcd for C28H24N2O4: C, 74.32; H, 5.35; N,
6.19. Found: C, 74.30; H, 5.38; N, 6.22.
[a]3D4ZC28.50 (c 0.66, CHCl3). UV/vis (CHCl3): lmax
(log 3)Z239 nm (10.9). FT-IR (KBr): 3090, 2980, 1620,
1505, 1460, 1220, 1190, 1130, 1100, 1080, 1030, 1000, 750,
1
725, 540 cmK1. H NMR (CDCl3, 300 MHz): d (ppm)Z
7.55–7.07 (m, 18H), 6.94 (br s, 2H), 5.02 (br s, 2H), 1.36 (d,
3H, JZ11.3 Hz), 1.14 (d, 3H, JZ11.0 Hz). 13C NMR
(CDCl3, 125 MHz): d (ppm)Z169.35, 143.34, 139.40,
136.86, 136.53, 129.90, 129.82, 128.88, 128.84, 128.19,
128.14, 127.56, 127.34, 126.59, 126.46, 49.51, 49.19, 22.18,
21.74. MS (FAB): m/z (%)Z449.6 (MHC, 90%), 471.5
(100%). Anal. Calcd for C30H30N2O2: C, 79.96; H, 6.71; N,
7.10. Found: C, 79.92; H, 6.82; N, 7.21.
4.4.4. Biphenyl-2,20-dicarboxylic acid bis-[(4-bezoic acid
ethyl ester)-amide] (3e). Light yellow gum. UV/vis
(CHCl3): lmax (log 3)Z237 nm (7.7). FT-IR (KBr): 2980,
2940, 1655, 1540, 1435, 1390, 1295, 1100, 770, 710,
565 cmK1. 1H NMR (CDCl3, 300 MHz): d (ppm)Z8.09 (br
s, 2H), 7.73–7.28 (m, 16H), 3.39 (q, 2H, JZ7.1 Hz), 3.30 (q,
2H, JZ7.1 Hz), 1.18 (t, 3H, JZ7.1 Hz), 1.12 (t, 3H, JZ
7.1 Hz). 13C NMR (CDCl3, 125 MHz): d (ppm)Z168.82,
168.51, 139.52, 138.29, 136.62, 125.69, 133.81, 133.46,
132.54, 130.65, 128.76, 126.09, 43.43, 14.71. MS (EI): m/z
(%)Z536.0 (MC, 20%), 330 (30%), 181 (100%). Anal.
Calcd for C32H28N2O6: C, 71.62; H, 5.25; N, 5.22. Found:
C, 71.54; H, 5.28; N, 5.34.
4.4.9. 3,30-Bipyridyl-6,60-dipivaloylamide (9). Off-white
solid; mp 167–169 8C. UV/vis (CHCl3): lmax (log 3)Z
298 nm (9.9). FT-IR (KBr): 3434, 2953, 2360, 1671, 1503,
1314, 1166, 827 cmK1 1H NMR (CDCl3, 300 MHz): d
.
(ppm)Z8.46 (d, 2H, JZ2.31 Hz), 8.34 (d, 2H, JZ8.76 Hz),
8.08 (bs, 2H), 7.88 (dd, 2H, JZ8.66 Hz), 1.35 (s, 18H). 13C
NMR (CDCl3, 125 MHz): d (ppm)Z177.51, 151.51,
145.91, 136.81, 129.67, 114.27, 40.24, 27.87. HRMS
(FAB): m/z calculated for C20H26N4O2 (MCNa)C:
377.1953; Found: 377.1952.
4.4.5. Biphenyl-2,20-dicarboxylic acid bis-pyridin-2-yl-
amide (3f). Light yellow gum. UV/vis (CHCl3): lmax
(log 3)Z280 (8.5), 238 nm (9.3). FT-IR (KBr): 3450, 3085,
1690, 1610, 1580, 1550, 1460, 1400, 1310, 1240, 790, 755,
4.4.10. 6,60-Dimethyl-2,20-bipyridyl (10). Cream colored
solid; mp 82–85 8C (lit.17 89–90 8C).
1
565 cmK1. H NMR (CDCl3, 300 MHz): d (ppm)Z8.03
(bs, 2H), 7.92–7.80 (m, 4H), 7.46–7.35 (m, 4H), 7.21–7.02
(m, 8H). MS (EI): m/z (%)Z366.4 (MC, 40%), 234 (100%).
Anal. Calcd for C24H18N4O2: C, 73.08; H, 4.60; N, 14.20.
Found: C, 73.00; H, 4.58; N, 14.24.
Acknowledgements
We acknowledge Department of Science and Technology
(DST), Council of Scientific and Industrial Research
(CSIR), Government of India for financial support,
and Professor Thomas Schrader of Philipps-Universitat,
Marburg, Germany for the mass spectra. A. K. A. and S. J.
thank CSIR, for research fellowships. J. F. G. thanks
Dublin City University for the purchase of a Siemens P4
diffractometer.
4.4.6. Biphenyl-2,20-dicarboxylic acid bis-[(6-methyl-
pyridin-2-yl)-amide] (3g). Light brown solid; mp 176–
178 8C (decomp). UV/cis (CHCl3): lmax (log 3)Z285 (9.6),
240 nm (10.0). FT-IR (KBr): 3450, 3080, 1690, 1610, 1580,
1540, 1460, 1400, 1310, 1240, 790, 755, 715, 565 cmK1. 1H
NMR (CDCl3, 200 MHz): d (ppm)Z8.97 (bs, 2H), 7.92 (d,
2H, JZ8.0 Hz), 7.70–7.68 (m, 2H), 7.53–7.38 (m, 6H),
7.24–7.21 (m, 2H), 6.80 (d, 2H, JZ7.4 Hz), 2.36 (s, 6H).
13C NMR (CDCl3, 125 MHz): d (ppm)Z168.52, 156.96,
150.93, 139.74, 139.02, 136.04, 130.87, 130.40, 128.39,
127.75, 119.70, 111.46, 22.90. MS (FAB): m/z (%)Z423.3
(MHC, 100%). Anal. Calcd for C26H22N4O2: C, 73.92; H,
5.25; N, 13.26. Found: C, 73.90; H, 5.30; N, 13.30.
References and notes
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NMR (CDCl3, 500 MHz): d (ppm)Z7.67–7.63 (m, 4H),
7.55–7.41 (m, 4H), 6.50–6.44 (m, 2H, 2!NH amide), 4.52–
4.48 (m, 1H), 4.23–4.19 (m, 1H), 4.01 (br s, 2H, OH), 3.75–
3.71 (m, 2H), 3.68–3.65 (m, 2H), 1.87–84 (m, 2H), 1.70–
1.63 (m, 2H), 1.07 (t, 3H, JZ4.9 Hz), 0.99 (t, 3H, JZ
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parameters, R-factor is 0.066, wR2Z0.126 [based on F2 for
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