Acid-induced conformational alteration of cis-preferential aromatic amides bearing N-methyl-N-(2-pyridyl) moiety

Article abstract of DOI:10.1016/j.tet.2011.08.085

A series of cis-preferential aromatic N-methyl amides was designed and synthesized, and acid-induced conformational alteration of these compounds was investigated by means of NMR measurements in solution and X-ray crystal structure analysis. Compounds with a terminal N-methyl-N-(2-pyridyl) amide unit showed acid-induced conformational change from cis to trans, while those with a terminal N-methyl-2-pyridinecarboxamide unit showed a change of the carbonyl orientation from anti to syn with retention of cis conformation.

Full text of DOI:10.1016/j.tet.2011.08.085

Tetrahedron 67 (2011) 8536e8543
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Acid-induced conformational alteration of cis-preferential aromatic amides
bearing N-methyl-N-(2-pyridyl) moiety
,
a
b
a
a
Iwao Okamoto a , Masayuki Terashima , Hyuma Masu , Mayumi Nabeta , Kaori Ono ,
*
Nobuyoshi Morita a, Kosuke Katagiri c, Isao Azumaya c, Osamu Tamura a
a Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan
b Chemical Analysis Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
c Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 August 2011
Received in revised form 29 August 2011
Accepted 29 August 2011
Available online 3 September 2011
A series of cis-preferential aromatic N-methyl amides was designed and synthesized, and acid-induced
conformational alteration of these compounds was investigated by means of NMR measurements in
solution and X-ray crystal structure analysis. Compounds with a terminal N-methyl-N-(2-pyridyl) amide
unit showed acid-induced conformational change from cis to trans, while those with a terminal N-
methyl-2-pyridinecarboxamide unit showed a change of the carbonyl orientation from anti to syn with
retention of cis conformation.
Keywords:
Pyridine
Ó 2011 Elsevier Ltd. All rights reserved.
Foldamer
Molecular switch
External stimulus responsive
Hydrogen bond
1. Introduction
cis
H3C
O
R''
The amide bond is one of the most important structural units for
constructing molecules or supramolecules,1 because it opens up the
possibility of cisetrans conformational change.2 Most aromatic
amides, such as benzanilide or acetanilide, favor trans structure,
whereas N-methylation of these compounds affords predominantly
cis-amides both in the crystal and in solution (Fig. 1).3 The use of
amide to control the relationship of aromatic functionalities of
a molecule permits spontaneous generation of chirality4 and the
formation of macrocyclic5 and other characteristic structures.6
Amide structure also has potential for use in molecular switches
and devices,7 and can work as an output control system, e.g., for
bioactivity,8 or as an external-stimulus-dependent functional con-
troller.9 We have developed several types of aromatic amides that
are responsive to redox control10 or solvent.11
N
H
N
N-methylation
R
R
O
R'
R'
trans
R''
Fig. 1. cis-Favored conformation of N-methyl aromatic amide.
Further, we have shown that conformational alteration of N-
methyl pyridyl amides can be induced by acid.15 It is important to
know whether this is a general phenomenon, and so in this work,
we designed and synthesized a series of cis-preferential aromatic
N-methyl amides, and systematically examined their acid-induced
conformational change by means of NMR measurements in solu-
tion and X-ray crystal structure analysis.
In this study, we focused on pyridine-containing aromatic am-
ides, which are found in many natural and synthetic bioactive
compounds. Pyridine works as a base and a ligand for metals,12 and
also as a switch for functional molecules,13 and we have already
examined pyridine-related dynamic folding and unfolding.14
2. Results and discussion
We synthesized aromatic amides 1e14 bearing 2-pyridyl and
2,6-pyridyl groups, as well as benzene and methyl derivatives for
reference (Fig. 2). Each amide was prepared from the corresponding
acid chloride or anhydride and amine under standard conditions.
The conformations and acid-induced conformational changes of
* Corresponding author. Tel./fax: þ81 42 721 1579; e-mail address: iokamoto@
ac.shoyaku.ac.jp (I. Okamoto).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.085

I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
8537
these aromatic N-methyl amides were investigated in the crystal
and in solution.
Amides 2 and 3 show similar structures to that of 1, with cis
conformation and pyridine orientation toward the amide func-
tionality. On the other hand, 4 takes a cisetrans structure about the
CH3
N
O
H3C
O
O
CH3
N
O
CH3
N
CH3
N
O
X1
X2
N
X2
N
N
X1
N
N
4: X2=N
5: X1=N
1: X1=X2=N
6: X2=CH
7: X1=CH
2: X1=N, X2=CH
3: X1=CH, X2=N
H3C
O
O
H3C
N
H3C
N
N
N
CH3
O
O
CH3
CH3
H3C
H3C
CH3
CH3
O
O
8
9
X2
X1
N
N
N
N
H3C
CH3
N
H
N
N
10: X2=N
11: X1=N
12: X2=CH
13: X1=CH
O
14
Fig. 2. Aromatic amides bearing 2-pyridyl moiety.
2.1. Conformational analyses using single-crystal X-ray
crystallography
two amide bonds, while 5 shows a cisecis structure. The two amide
carbonyl groups in 4 and 5 lie in the anti orientation to the pyridine
nitrogen atom, because of dipoleedipole interaction, so that cise-
trans conformation of 4 is favored to avoid steric repulsion between
the two terminal pyridine rings.
X-ray crystallographic analysis was conducted to establish the
crystal structures of these amides. The crystal structures of amides
1e7 are illustrated in Fig. 3.
Fig. 3. Crystal structures of amides and their salts.a Counter anions of salts are omitted for clarity.b
aCrystallographic data of compound 1, 4, 5, 4H, and 5H were reported in our previous paper.15
bPerchlorates 1H, 4H, 5H, 6H, and 7H contain a 1:2 ratio of amide and HClO4, whereas 2H and 3H contain a 1:1 ratio of amide and HClO4.
cThe crystals of 1H, 4H, and 6H contain two types of conformers or disordered molecules. In the figure, representative structures are shown.
dThe crystal of 7 includes water molecules. Hydrogen bonds between pyridyl nitrogen and water oxygen are indicated as black dotted lines.
Amide 1 shows the characteristic structural feature of aromatic
N-methyl amides, that is, the two aromatic rings are located in a cis
relationship. The nitrogen of the C-pyridine ring lies in the anti
orientation to the carbonyl oxygen (Fig. 4).
Amides 6 and 7 take characteristic cisecis structure linked by
the central benzene ring. The crystal of 7 includes water molecules,
and hydrogen bonding between the water molecules and pyridyl
moieties results in a symmetrical conformation.

8538
I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
cis
N
anti
N
O
CH3
H3C
H3C
N
N
N
N
N
N
cis
O
trans
O
anti
anti
1
4
Fig. 4. Crystal structure of amides 1 and 4.
In order to investigate the crystal structures of these amides in
an acidic environment, the perchloric acid salts were prepared.
Addition of perchloric acid to a solution of amide 1 in ethyl acetate
gave a precipitate, which was recrystallized to afford the salt 1H.
Elemental analysis revealed that the salt 1H contains 1 and
perchloric acid in 1:2 ratio. Other amides 2e7 also gave the cor-
responding perchlorates, and recrystallization afforded 2He7H.
Their crystal structures are also shown in Fig. 3.
Unfortunately, well-ordered crystals of 1H and 2H have not been
obtained to date, but the data presented here suggest that confor-
mational transformation does occur. That is, the addition of acid to
1 caused both pyridine rings to become protonated, leading to
conformational change from cis to trans because of N-pyridine
protonation, and from anti to syn because of C-pyridine protonation
(Fig. 5).
Fig. 6. 1H NMR spectra of aromatic protons of amides 1 and 14 at various temperatures
in CD2Cl2.
in cis conformation, like many other aromatic N-methyl amides
(Fig. 7).3
H3C
N
O
CH3
N
N
N
N
H
H
N
H
H
O
H
H
in CD2Cl2
H
H
C-Pyridine
cis-favored
cis
O
anti
syn
Fig. 7. Conformational preference of amide 1 in solution.
H
N
H3C
N
N
O
H
N
N
In order to examine the acid-induced structures in solution, the
1H NMR spectra of 4 in the presence of acid were measured.15
Fig. 8 shows the spectra of 4, 4H, 4 with excess TFA-d, and 4 with
excess DClO4. Although these conformational studies are discussed
about solution in dichloromethane, the salts of 4 with DClO4 was
not soluble enough in CD2Cl2. In order to compare the effects of
acids, the spectra in Fig. 8 were measured in CD3CN. Protonation of
the amide 4 caused a lower-field shift of aromatic proton signals,
and addition of perchloric acid-induced greater shifts than did TFA.
Comparison of spectrum b with c indicates that excess TFA induces
conversion from 4 to 4H, that is, excess TFA protonates the terminal
pyridines of 4, while excess perchloric acid caused further pro-
tonation. These results suggested that it would be appropriate to
carry out the 1H NMR study using CD2Cl2 as the solvent, and TFA-
d as the acid additive.
H+
N
H3C
trans
N-Pyridine
1
1H
Fig. 5. Conformational transformation of amide 1.
The results for 2H support the idea that N-pyridine protonation
causes cisetrans transformation, and those for 3H confirm that C-
pyridine protonation causes antiesyn transition.
The crystal structures of 4H and 5H indicate that protonation
occurs at the two terminal pyridines prior to the central pyridine,
even though the central pyridine of 5 is electron-rich. These pro-
tonations influence the conformation in the same way as in 1e3,
that is, 4H takes transetrans structure, while 5H takes cisecis and
syn structure. Similar changes are seen in the structures of 6H and
7H.
2.2. Conformational analyses in solution using NMR study
The structures of the amides in solution were analyzed by
means of 1H NMR measurement. While the spectrum of 1 at room
temperature shows a single set of signals because of fast equilib-
rium between cis and trans conformations, lowering the temper-
ature caused peak broadening, followed by the appearance of two
sets of signals (Fig. 6). Arrows show signals of the minor conformer
observed at ꢀ90 ꢁC.
Fig. 8. 1H NMR spectra of (a) amide 4; (b) 4H; (c) 4 with TFA-d (150 equiv); (d) 4 with
DClO4 (30 equiv) in CD3CN.
The aromatic proton signals of the cis conformer were shifted
upfield from those of the trans conformer because of the shielding
effect of the aromatic rings. Comparison of the spectrum at ꢀ90 ꢁC
with the spectrum of NeH amide 14, which exists in trans confor-
mation,16 indicates that the N-methyl pyridyl amide 1 exists mainly
The chemical shifts of aromatic protons of amides 1e13 and
their change upon addition of TFA-d are summarized in Table 1. It is

I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
8539
Table 1
Chemical shifts of aromatic protons and lower-field shifts caused by the addition of TFA-da
H-a H-b H-c H-d H-e
þ1.2 þ0.4
H-a0
H-b0
þ1.1
H-c0
H-d0
þ0.8
H-e0
1b
2
6.98
6.86
7.08
7.00
6.75
6.79
6.84
7.29
þ0.9
þ0.9
7.52
7.44
7.20
7.56
7.39
7.47
7.02
7.72
7.01
7.02
7.13
7.04
þ0.9
þ0.8
þ0.4
þ0.8
8.27
8.38
7.63
7.29
7.41
7.58
7.60
7.20
7.37
þ0.7
7.72
7.21
7.62
7.75
7.73
7.05
7.62
7.21
7.32
7.16
þ1.1
8.27
8.33
8.31
8.31
8.55
þ1.2
þ0.3
þ1.0
þ0.6
þ1.2
þ0.7
þ0.8
þ0.1
þ0.3
þ0.2
0
þ0.4
ꢀ0.1
þ0.5
0
þ0.4
þ0.7
þ0.5
þ0.7
þ0.8
dc
þ0.4
þ0.9
3
þ0.2
þ0.7
þ0.6
þ1.0
þ0.6
þ0.3
þ0.6
þ0.6
þ0.6
þ0.5
4b
5b
6
8.25
8.37
8.44
7.24
7.12
7.31
þ0.8
þ1.0
þ1.0
7.03
7.15
þ0.8
þ0.6
þ0.7
7.35
7.37
þ0.7
7
8
9
10
11
12
13
6.81
7.07
þ0.6
þ0.2
dc
7.54
7.61
þ0.8
þ0.1
7.77
7.89
þ1.0
þ0.2
7.24
7.17
0
7.76
7.44
þ0.6
þ0.3
7.40
þ0.3
7.40
þ0.3
þ0.2
þ0.3
The aromatic proton is marked as follows:
CH3
N
O
e'
X2
e
X1
d'
c'
d
a'
c
a
b'
b
a
b
c
These values are recorded in ppm. In every case, 3e5 mg of amide in 0.5 mL of CD2Cl2 was used, and 150 equiv of TFA-d was added.
Compounds 1, 4 and 5 were reported in our previous paper.15
The change could not be measured because of peak broadening.
natural that these N-methyl amides have broadly similar chemical
shifts to each other, but some important differences were observed.
To analyze the conformational change of the basic structure 1 in
terms of changes of the N-pyridine unit and C-pyridine unit, these
chemical shifts and changes were considered in detail.
H
O
N
O
H3C
N
X2
X2
H+
N
N
Ha
Ha
H3C
Chemical shifts and shift changes of H-a, b, c and H-d of 2 are in
good accordance with those of 1, so 2 can be considered to be
representative of the N-pyridine unit of 1. Chemical shifts of 8, an N-
methyl amide without the C-aromatic ring, and 2 show clear dif-
ferences at H-a, 7.29 and 6.86, indicating that the benzoyl group of 2
causes a high-field shift in 2. The protonation of 8 changes the
chemical shift of H-a by þ0.3, while the change in 2 was þ0.9. This
large lower-field shift indicates disappearance of high-field shift,
that is, it reflects conformational change from cis to trans (Fig. 9).
The resulting coordination mode is similar to chelation of NeH type
trans amide.17 However, this type of hydrogen bonding in these N-
methyl amides is different from the well-known interaction in NeH
pyridyl oligo amides,13a,18 because our amides lack amide hydrogen,
and originally favor cis conformation.
4: X2=N
6: X2=CH
Fig. 10. Conformational change of amides 4 and 6.
does not experience high-field shift from the terminal aromatic
group, that is, 4 takes cis conformation along with anti-preferential
carbonyl orientation (Fig. 11). Isophthaloyl amide 6 has smaller
chemical shifts of H-a0 and H-b0 than 12. In this amide 6, the car-
bonyl orientation is less strained around the central benzene ring
compared to pyridine.
N
cis
O
CH3
cis
N
CH3
N
CH3
H3C
Ha
N
N
N
N
O
O
Ha'
N
H+
Hb'
anti
Ha'
Ha
N
O
Hb'
H
6
2
4
Fig. 11. Conformations of 4 and 6.
CH3
N
H3C
N
Ha
N
O
These similarities in chemical shifts and conformational
changes show a general tendency that a terminal N-pyridine unit of
N-methylamide works as a cisetrans conformational switching
unit upon addition of acid (Fig. 12).
CH3
H+
CH3
Ha
8
N
O
H
Fig. 9. Conformational change of amides 2 and 8.
cis
CH3
H
H+
Similar effects were observed in the N-pyridine unit of 4 and 6,
suggesting that these amides 4 and 6, with two N-methyl amide
functionalities, change their conformation from cisecis to trans-
etrans upon addition of acid (Fig. 10).
O
N
O
N
N
N
CH3
trans
On the other hand, the central parts of 4 and 10 have similar
chemical shift values. This shows that the central pyridine ring of 4
Fig. 12. Conformational change of N-pyridine unit.

8540
I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
The effect of carbonyl orientation can be seen more clearly in the
anti
O
O
H
N
C-pyridine terminal unit. Chemical shifts of the C-pyridine unit in 3
are in good accordance with those of 1, whereas the chemical shift
changes are not. The important structural difference between 3 and
1 is the N-aromatic part, that is, 3 cannot be conformationally
switched because it lacks nitrogen on the N-aromatic unit. Com-
parison with 9 shows a characteristic change in H-a0, that is, al-
though the pyridine ring is considered to be protonated, the H-
a0 proton on the pyridine ring of 3 shows a higher-field shift. This
clearly indicates conformational change from anti to syn orienta-
tion around the carbonylepyridine bond of 3 (Fig. 13).
H+
H3C
H3C
N
N
N
syn
Fig. 15. Conformational change of C-pyridine unit.
3. Conclusion
N-Methyl aromatic amides bearing a 2-pyridyl group show
conformational switching upon acid addition. The terminal C-(2-
pyridyl) unit undergoes a change in carbonyl orientation, and the
terminal N-(2-pyridyl) unit shows a change from cis to trans con-
formation. These structural features and alterations appear to be
general for N-methyl pyridyl amides. Thus, the conformation of the
terminal amide-(2-pyridyl) moiety can be switched by the use of an
appropriate acid.
O
O
H
N
Ha'
H3C
H3C
N
N
H+
N
Ha'
3
O
O
H
N
Ha'
H3C
H3C
4. Experimental section
4.1. General
N
H3C
N
H3C
H+
N
Ha'
9
Melting points were determined by using a Yanaco melting
point apparatus MP-S3 and are uncorrected. Elemental analyses
were carried out on Thermo Finnigan Flash EA1112, and antipyrine
was used as a standard. 1H and 13C NMR spectra were recorded on
a JEOL AL-300, and chemical shifts are expressed in parts per mil-
lion relative to tetramethylsilane. IR spectra were recorded on
a Shimadzu FTIR-8200A. Mass spectra were measured on a JEOL
Fig. 13. Conformational change of amides 3 and 9.
The behavior of N-methyl amides with three aromatic rings is
consistent with the general trend of these conformational changes.
Chemical shift comparison of H-a in 5 and H-a in 11 indicates
cisecis-favored conformation of 5, based on the high-field shift
caused by the terminal pyridine rings. Similar findings for H-a in 7
and 13 can also be considered as evidence for cisecis conformation.
Comparison of the C-pyridine unit of 5 and 7 with that of 3 shows
a similar structural trend. In the case of H-a0 of 5, the lower-field
shift upon addition of acid is absent. This terminal 2-pyridine car-
boxylic unit should behave similarly, that is, its orientation should
be changed from anti to syn, with unchanged cis conformation
(Fig. 14).
MS700 or HX110. Silica gel [silica gel 40e50
mm neutral (Kanto
Chemical Co., Inc.)] was used for all chromatographic procedures.
4.1.1. N-Methyl-N-(2-pyridyl)-2-pyridinecarboxamide (1). To a mix-
ture of picolinic acid (617 mg, 5.00 mmol), triethylamine (1.37 mL,
10.0 mmol), and THF (15 mL), ethyl chloroformate (0.48 mL,
5.00 mmol) was added. The mixture was stirred at ambient tem-
perature for 1.5 h, then 2-(methylamino)pyridine (0.52 mL,
5.00 mmol) was added and stirring was continued for 1 h. The
solvent was evaporated in vacuo to give the crude product, which
was purified by flash chromatography (ether) to give 1 (594 mg,
56%) as pale brown prisms. Mp 77.5 ꢁC (AcOEt/hexane); [Anal.
Found: C, 67.51; H, 5.22; N, 19.52. C12H11N3O requires C, 67.59; H,
CH3
N
CH3
N
X1
O
X1
O
N
H+
H
Ha'
Ha'
a N
H
5: X1=N
7: X1=CH
5.20; N, 19.71%]; nmax (KBr) 1655, 1587, 1568 cmꢀ1
;
1H NMR
(300 MHz, CD2C12) 8.27 (2H, m), 7.72 (1H, dt, J 1.7, 7.9 Hz), 7.63
d
(1H, dt, J 7.9, 1.3 Hz), 7.52 (1H, dt, J 2.0, 8.1 Hz), 7.21 (1H, ddd, J 7.5,
4.8, 1.5 Hz), 7.01 (1H, ddd, J 7.5, 4.9, 1.1 Hz), 6.98 (1H, br d, J 8.2 Hz),
CH3
3.54 (3H, s); 13C NMR (75 MHz, CDC13)
d 169.1, 156.6, 154.0, 148.2,
X1
N
O
148.0, 137.4, 136.6, 124.3, 124.0, 120.8, 120.0, 35.9; m/z (EI) 213.
CH3
Ha
4.1.2. N-Methyl-N-(2-pyridyl)benzamide (2). A mixture of 2-
(methylamino)pyridine (1.0 mL, 9.73 mmol), pyridine (20 mL), and
benzoyl chloride (2.2 mL, 19.5 mmol) was stirred at ambient tem-
perature for 17 h. After the addition of water, the mixture was
poured into satd NaHCO3 solution, and extracted with CH2Cl2. The
organic solution was washed with brine, dried over MgSO4, and
evaporated in vacuo to give the crude product, which was purified
by flash chromatography (AcOEt/hexane 1:2) to afford 2 (1.92 g,
93%) as a colorless solid. Mp 41.5e43.0 ꢁC (hexane); [Anal. Found: C,
73.38; H, 5.72; N, 13.17. C13H12N2O requires C, 73.57; H, 5.70; N,
11: X1=N
13: X1=CH
Fig. 14. Conformations of amides 5, 7, 11, and 13.
Unfortunately, amide 7 with similar terminal structure showed
marked peak broadening upon addition of acid, but the chemical
shifts and changes of H-c0 and H-d0 signals suggest similar confor-
mational behavior.
Overall, these results indicate that the terminal C-pyridine of N-
methyl amide works as an acid-induced antiesyn rotation unit, but
cis conformation of the N-methyl amide moiety is retained if TFA is
used as the inducing acid (Fig. 15).
13.20%]; nmax (KBr) 1649, 1585, 1359 cmꢀ1
;
1H NMR (300 MHz,
CD2C12) 8.38 (1H, ddd, J 0.9, 2.0, 4.9 Hz), 7.44 (1H, dt, J 2.0, 7.5 Hz),
d
7.32 (1H, m), 7.29 (2H, m), 7.21 (2H, m), 7.02 (1H, ddd, J 1.0, 5.0, 7.5),
6.86 (1H, dt, J 8.0, 0.9 Hz), 3.51 (3H, s); 13C NMR (75 MHz, CDC13)

I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
8541
d
170.9, 156.7, 148.7, 137.3, 136.0, 130.1, 128.5, 128.0, 121.5, 120.8,
The mixture was filtered and the filtrate was evaporated in vacuo to
give the crude product, which was purified by flash chromatogra-
phy (AcOEt) to afford 7 (351 mg, 46%) as a colorless solid. Re-
crystallization from CH2Cl2/AcOEt gave colorless prisms; mp
165.0e166.0 ꢁC; [Anal. Found: C, 69.41; H, 5.24; N, 15.98.
C20H18N4O2 requires C, 69.35; H, 5.24; N, 16.17%]; nmax (KBr) 1649,
35.9; m/z (EI) 212.
4.1.3. N-Methyl-N-phenyl-2-pyridinecarboxamide (3). To a mixture
of picolinic acid (2.27 g, 18.4 mmol), triethylamine (5.12 mL,
36.8 mmol), and THF (60 mL), ethyl chloroformate (1.76 mL,
18.4 mmol) was added. The mixture was stirred at ambient tem-
perature for 2 h, then N-methylaniline (2.0 mL, 18.4 mmol) was
added and stirring was continued for 22 h. The solvent was evap-
orated in vacuo to give the crude product, which was purified by
flash chromatography (AcOEt/hexane 2:1) to afford 3 (1.75 g, 45%)
as colorless needles. Mp 47.0e50.5 ꢁC (hexane); [Anal. Found: C,
73.60; H, 5.64; N, 12.97. C13H12N2O requires C, 73.57; H, 5.70; N,
1598, 1589, 1568 cmꢀ1; 1H NMR (300 MHz, CD2C12)
d 8.31 (2H, m),
7.62 (2H, dt, J 1.7, 7.7 Hz), 7.37 (2H, m), 7.12 (2H, ddd, J 1.1, 4.9,
7.7 Hz), 7.02 (1H, m), 6.84e6.81 (3H, m), 3.29 (6H, s); 13C NMR
(75 MHz, CDC13)
d 168.4, 153.9, 148.3, 144.8, 136.4, 129.2, 124.7,
124.5, 124.0, 123.6, 37.9; m/z (EI) 346.
4.1.8. N-Methyl-N-(2-pyridyl)acetamide (8). A mixture of 2-(meth-
ylamino)pyridine (857 mg, 7.92 mmol) and acetic anhydride
(4.23 g, 41.4 mmol) was heated at 70 ꢁC for 4 h. After removal of the
solvent under reduced pressure, chromatography (AcOEt) of the
residue gave 8 as a pale brown oil in quantitative yield. nmax (KBr)
13.20%]; nmax (KBr) 1654, 1583, 1380 cmꢀ1
CD2C12) 8.33 (1H, br s), 7.62 (1H, br t, J 7.2 Hz), 7.41 (1H, br d, J
7.5 Hz), 7.20 (1H, m), 7.16 (1H, m), 7.13 (1H, m), 7.08 (1H, m), 3.45
(3H, s); 13C NMR (75 MHz, CDC13)
168.7, 154.3, 148.4, 144.3, 136.1,
;
1H NMR (300 MHz,
d
d
128.9, 126.6, 126.4, 123.8, 123.6, 38.0; m/z (EI) 212.
1663, 1587, 1379 cmꢀ1; 1H NMR (300 MHz, CD2C12)
d 8.44 (1H, ddd,
J 0.8, 2.0, 4.8 Hz), 7.72 (1H, dd, J 2.0, 7.5 Hz), 7.29 (1H, d, J 8.1 Hz), 7.15
4.1.4. N,N0-Dimethyl-N,N0-di(2-pyridyl)-2,6-pyridinedicarboxamide
(4). Using the same method as above, 4 was obtained from pyri-
dine-2,6-carbonyldichloride (1.0 g, 4.9 mmol), triethylamine
(2.7 mL, 19.6 mmol), and 2-(methylamino)pyridine (1.10 mL,
10.8 mmol). Chromatography (AcOEt) afforded a colorless solid
(813 mg, 48%). Mp 113 ꢁC (AcOEt/hexane); [Anal. Found: C, 65.83; H,
4.86; N, 20.23. C19H17N5O2 requires C, 65.69; H, 4.93; N, 20.16%];
nmax (KBr) 1666, 1645, 1585, 1483, 1435, 1420, 1377, 1296 cmꢀ1; 1H
(1H, ddd, J 1.0, 4.8, 7.3 Hz), 3.31 (3H, s), 2.03 (3H, s); 13C NMR
(75 MHz, CDC13, 55 ꢁC)
d 170.7, 156.5, 148.9, 138.0, 121.5, 120.3, 35.4,
23.0; m/z (EI) 150; HRMS (EI): Mþ, found 150.0807. C8H10N2O re-
quires 150.0794.
4.1.9. N,N-Dimethyl-2-pyridinecarboxamide (9). A mixture of pico-
linic acid (322 mg, 2.62 mmol), thionyl chloride (5.0 g, 42 mmol)
and a small amount of DMF was heated at reflux for 3 h, then
volatile materials were removed under reduced pressure. The
resulting crude acid chloride was dissolved in 5 mL of THF, and
added slowly to dimethylamine (2.0 g, 44 mmol) at ꢀ78 ꢁC, fol-
lowed by stirring in a sealed tube at ambient temperature for 18 h.
The resulting mixture was poured into satd NaHCO3 solution, and
extracted with CH2Cl2 The organic solution was washed with brine,
dried over MgSO4, and evaporated in vacuo to give the crude
product, which was purified by flash chromatography (AcOEt) to
afford 9 (328 mg, 84%) as a pale yellow oil. nmax (KBr) 1637, 1538,
NMR (300 MHz, CD2C12) d 8.25 (2H, ddd, J 5.0, 2.0, 0.9 Hz), 7.75 (1H,
dd, J 8.3, 7.2 Hz), 7.58 (2H, d, J 7.3 Hz), 7.56 (2H, dt, J 2.0, 7.3 Hz), 7.04
(2H, ddd, J 7.5, 5.0, 1.1 Hz), 7.00 (2H, br d, J 7.9 Hz), 3.34 (6H, s); 13C
NMR (75 MHz, CDC13) d 168.0,156.0,152.2, 148.0,137.5, 137.4, 124.8,
120.9, 120.1, 35.8; m/z (EI) 347.
4.1.5. 2,6-Bis(N-methyl-2-pyridinecarboxamido)pyridine (5). Using
the same method as above, 5 was obtained from picolinic acid
(1.0 g, 8.13 mmol), thionyl chloride (4.0 mL, 56 mmol), triethyl-
amine (1.70 mL, 12.2 mmol), and 15 (557 mg, 4.07 mmol). Chro-
matography (AcOEt) afforded a colorless solid (232 mg, 17%). Mp
140.0e140.5 ꢁC (AcOEt/hexane); [Anal. Found: C, 66.07; H, 4.94; N,
20.19. C19H17N5O2 requires C, 65.69; H, 4.93; N, 20.16%]; nmax (KBr)
1398 cmꢀ1; 1H NMR (300 MHz, CD2C12)
dt, J 1.7, 7.7 Hz), 7.54 (1H, d, J 7.7 Hz), 7.31 (1H, ddd, J 0.8, 5.0, 7.7 Hz),
d 8.55 (1H, br s), 7.77 (1H,
3.03 (6H, s); 13C NMR (75 MHz, CDC13)
d 168.8, 154.4, 148.1, 136.8,
124.2, 123.3, 38.8, 35.5; m/z (EI) 150; HRMS (EI): Mþ, found
1672, 1649, 1585, 1570 cmꢀ1
;
1H NMR (300 MHz, CD2C12)
d
8.31
150.0784. C8H10N2O requires 150.0794.
(2H, dd, J 5.9, 1.1 Hz), 7.73 (2H, dt, J 1.7, 7.9 Hz), 7.60 (2H, dt, J 7.9,
1.3 Hz), 7.39 (1H, t, J 7.9 Hz), 7.24 (2H, m), 6.75 (2H, d, J 7.9 Hz), 3.23
d 169.2, 154.7, 154.1, 148.1, 138.8,
136.7, 124.5, 124.0, 115.7, 35.3; m/z (EI) 347.
4.1.10. N,N,N0,N0-Tetramethyl-2,6-pyridinedicarboxamide (10). Using
the same method as above, 10 was obtained from 2,6-
pyridinedicarbonyl dichloride (529 mg, 2.59 mmol) and dimethyl-
amine (2.75 g, 61 mmol). Colorless plates (406 mg, 71%). Mp
144.5e148.0 ꢁC (AcOEt); [Anal. Found: C, 59.62; H, 6.84; N, 18.87.
C11H15N3O2 requires C, 59.71; H, 6.83; N, 18.99%]; nmax (KBr) 1635,
(6H, s); 13C NMR (75 MHz, CDC13)
4.1.6. N,N0-Dimethyl-N,N0-di(2-pyridyl)-1,3-benzenedicarboxamide
(6). Using the same method as above, 6 was obtained from iso-
phthalic acid (600 mg, 3.61 mmol), thionyl chloride (5.0 mL,
70 mmol), triethylamine (1.97 mL, 14.4 mmol), and 2-(methyl-
amino)pyridine (0.74 mL, 7.22 mmol). Chromatography (CH2Cl2/
1508, 1421 cmꢀ1; 1H NMR (300 MHz, CD2C12)
7.61 (2H, d, J 7.7 Hz), 3.09 (6H, s), 3.02 (6H, s); 13C NMR (75 MHz,
CDC13,) 168.2, 153.1, 138.0, 123.9, 39.0, 35.6; m/z (EI) 221.
d 7.89 (1H, t, J 7.7 Hz),
d
AcOEt 1:1) afforded
a colorless solid (673 mg, 54%). Mp
149.5e151.0 ꢁC (AcOEt/hexane); [Anal. Found: C, 69.25; H, 5.18; N,
16.02. C20H18N4O2 requires C, 69.35; H, 5.24; N, 16.17%]; nmax (KBr)
4.1.11. 2,6-Bis(N-methylacetamido)pyridine (11). Using the same
method as above,11 was obtained from 15 (100 mg, 0.73 mmol) and
acetic anhydride (2 mL, 21 mmol). Pale brown oil (90 mg, 55%). nmax
1645, 1585 cmꢀ1; 1H NMR (300 MHz, CD2C12)
d 8.37 (2H, ddd, J 0.8,
2.0, 4.9, Hz), 7.47 (2H, m), 7.35 (1H, m), 7.20 (2H, dd, J 1.5, 7.3 Hz),
(KBr) 1670,1522,1375 cmꢀ1; 1H NMR (300 MHz, CD2C12)
d
7.76 (1H,
7.05 (1H, m), 7.03 (2H, m), 6.79 (2H, d, J 8.1 Hz), 3.43 (6H, s); 13C
t, J 7.9 Hz), 7.24 (2H, d, J 7.7 Hz), 3.34 (6H, s), 2.12 (6H, s); 13C NMR
NMR (75 MHz, CDC13)
128.6, 127.7, 121.3, 121.0, 35.9; m/z (EI) 346.
d
169.9, 156.3, 148.8, 137.4, 136.2, 129.9,
(75 MHz, CDC13) d 170.7, 154.6, 139.7, 117.0, 35.3, 23.4; m/z (EI) 221;
HRMS (EI): Mþ, found 221.1167. C11H15N3O2 requires 221.1164.
4.1.7. 1,3-Bis(N-methyl-2-pyridinecarboxamido)benzene (7). To
a
4.1.12. N,N,N0,N0-Tetramethyl-1,3-benzenedicarboxamide (12). Using
the same method as above, 12 was obtained from isophthaloyl
chloride (520 mg, 2.56 mmol) and dimethylamine (10 mL,
153 mmol). Pale yellow solid (442 mg, 78%). Mp 125.0e129.0 ꢁC
(AcOEt/hexane); [Anal. Found: C, 65.54; H, 7.38; N, 12.47.
C12H16N2O2 requires C, 65.43; H, 7.32; N, 12.72%]; nmax (KBr) 1631,
solution of picolinic acid (543 mg, 4.41 mmol) in tetrahydrofuran,
triethylamine (0.90 mL, 6.60 mmol) and ethyl chloroformate
(0.42 mL, 4.41 mmol) were added, and the mixture was stirred at
ambient temperature for 1 h. A solution of 16 (300 mg, 2.20 mmol)
in tetrahydrofuran was added and stirring was continued for 13 h.

8542
I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
1502, 1398 cmꢀ1
;
1H NMR (300 MHz, CD2C12)
d
7.40 (3H, m), 7.37
After addition of methanol with cooling, 10% HCl was added, and
(1H, m), 2.96 (12H, s); 13C NMR (75 MHz, CDC13)
d
170.7, 136.5,
the mixture was basified with 10% NaOH aq, then extracted with
CH2Cl2. The organic layer was washed with brine, dried over
MgSO4, and evaporated in vacuo to give the crude product, which
was purified by flash chromatography (CH2Cl2/AcOEt 20:1) to af-
ford 16 (924 mg, 74%) as a yellow oil. 1H NMR (300 MHz, CDCl3)
128.5, 128.1, 125.6, 39.5, 35.3; m/z (EI) 220.
4.1.13. 1,3-Bis(N-methylacetamido)benzene (13). Using the same
method as above, 13 was obtained from 16 (100 mg, 0.73 mmol)
and acetic anhydride (2 mL, 21 mmol). Colorless solid (151 mg,
94%). Mp 153.0e157.5.0 ꢁC (toluene); [Anal. Found: C, 65.33; H,
7.46; N, 12.53. C12H16N2O2 requires C, 65.43; H, 7.32; N, 12.72%];
d
6.99 (1H, t, J 8.1 Hz), 6.02 (2H, dd, J 2.2, 8.1 Hz) 5.88 (1H, t, J 2.2 Hz),
2.80 (6H, s); m/z (EI) 136; HRMS (EI): Mþ, found 136.1006. C8H12N2
requires 136.1000.
nmax (KBr) 1650, 1494, 1350 cmꢀ1 1H NMR (300 MHz, CD2C12)
;
d
7.44 (1H, t, J 7.9 Hz), 7.17 (2H, d, J 8.3 Hz), 7.07 (1H, t, J 1.8 Hz), 3.23
4.2. General procedure for perchlorate preparation
(6H, s), 1.86 (6H, s); 13C NMR (75 MHz, CDC13, 55 ꢁC)
d 169.9, 145.9,
130.7, 125.9, 125.8, 37.3, 22.3; m/z (EI) 220.
To a solution of amide 1e7 in ethyl acetate, 60% perchloric acid
was added at ambient temperature to give the corresponding
perchlorate. The salt was collected by filtration and recrystallized.
Perchlorate 1H (1þ2HClO4): Mp 217.0e221.0 ꢁC (recryst from
CH3CN/CH2Cl2, colorless rods). Anal. Found: C, 34.97; H, 2.92; N,
9.97. C12H13N3Cl2O9 requires C, 34.80; H, 3.16; N, 10.15%.
4.1.14. N-(2-Pyridyl)-2-pyridinecarboxamide (14). Using the same
method as above, 14 was obtained from picolinic acid (394 mg,
3.20 mmol), thionyl chloride (6.36 g, 54 mmol), 2-aminopyridine
(251 mg, 2.67 mmol). Chromatography (AcOEt/hexane 1:4 then
1:2) afforded 14 as colorless needles (232 mg, 42%). Mp
118.5e120.5 ꢁC (AcOEt/hexane); [Anal. Found: C, 66.23; H, 4.51; N,
20.98. C11H9N3O requires C, 66.32; H, 4.55; N, 21.09%]; nmax (KBr)
Perchlorate 2H (2þHClO4): Mp 128.0e129.0 ꢁC (recryst from
AcOEt/hexane, powder). Anal. Found: C, 49.84; H, 3.86; N, 8.63.
C13H13N2ClO5 requires C, 49.93; H, 4.19; N, 8.96%.
3348, 1692, 1304 cmꢀ1; 1H NMR (300 MHz, CD2C12)
d
10.45 (1H, br
Perchlorate 3H (3þHClO4): Mp 219.0e221.0 ꢁC (recryst from
AcOEt, colorless powder). Anal. Found: C, 49.68; H, 3.96; N, 8.75.
C13H13N2ClO5 requires C, 49.93; H, 4.19; N, 8.96%.
s), 8.66 (1H, ddd, J 4.8, 1.8, 1.1 Hz), 8.39 (1H, dt, J 8.4, 1.1 Hz), 8.36
(1H, ddd, J 5.9,1.8,1.1 Hz), 8.27 (1H, dt, J 7.7,1.1 Hz), 7.94 (1H, dt, J 1.8,
7.7 Hz), 7.77 (1H, dt, J 1.5, 7.9 Hz), 7.53 (1H, ddd, J 7.3, 4.8, 1.1 Hz),
Perchlorate 4H (4þ2HClO4): Mp 196.5e198.0 ꢁC (recryst from
CH3CN/AcOEt, colorless prisms). Anal. Found: C, 41.87; H, 3.31; N,
12.77. C19H19N5Cl2O10 requires C, 41.62; H, 3.49; N, 12.77%.
Perchlorate 5H (5þ2HClO4): Mp 170.5e173.0 ꢁC (recryst from
CH3CN/AcOEt, colorless prisms). Anal. Found: C, 41.59; H, 3.27; N,
12.47. C19H19N5Cl2O10 requires C, 41.62; H, 3.49; N, 12.77%.
Perchlorate 6H (6þ2HClO4): Mp 214.0e216.5 ꢁC (recryst from
CH3CN/EtOH, colorless prisms). Anal. Found: C, 43.81; H, 3.54; N,
10.04. C20H20N4Cl2O10 requires C, 43.89; H, 3.68; N, 10.24%.
Perchlorate 7H (7þ2HClO4): Mp 251.0e253.0 ꢁC(dec) (recryst
from CH3CN/EtOH, colorless prisms). Anal. Found: C, 43.70; H, 3.55;
N, 10.05. C20H20N4Cl2O10 requires C, 43.89; H, 3.68; N, 10.24%.
7.09 (1H, ddd, J 7.3, 4.8, 1.1 Hz); 13C NMR (75 MHz, CDC13)
d 162.6,
151.2, 149.3, 148.2 (overlapped), 138.2, 137.5, 126.7, 122.4, 119.8,
113.9; m/z (EI) 199.
CH3
HN
CH3
NH
CH3
HN
CH3
NH
N
15
16
4.1.15. N,N0-Dimethyl-2,6-diaminopyridine (15). A mixture of 2,6-
dibromopyridine (25.0 g, 105.5 mmol) and 40% methylamine so-
lution in water (100 mL) was heated in a sealed tube at 190 ꢁC for
17 h. After cooling, the solution was filtered and the filtrate was
diluted with water (400 mL), then extracted with CH2Cl2. The or-
ganic layer was washed with brine, dried over MgSO4, and evapo-
rated in vacuo to give the crude product, which was purified by
flash chromatography (CH2Cl2 then AcOEt/hexane 1:1) to afford 15
(11.76 g, 81%) as a pale brown solid. This was used without further
purification for syntheses. Mp 70.5 ꢁC (AcOEt/hexane); 1H NMR
4.3. Single-crystal X-ray crystallography
Crystallographic data were collected on a four-circle diffrac-
ꢀ
tometer with Cu K
diffractometer with Mo K
a
(
l
¼1.54178 A) radiation (for 7H) or on a CCD
ꢀ
a
(
l
¼0.71073 A) radiation (for other
compounds). Data collections were carried out at low temperature
(120e150 K) using liquid nitrogen. All of the crystal structures were
solved by direct methods with SHELXS-97 and refined with full-
matrix least-squares SHELXL-97.19 All non-hydrogen atoms were
refined anisotropically. Hydrogen atoms of the amides were in-
cluded at their calculated positions. Hydrogen atoms of water
molecules (for 7) were determined based on the electron density
distribution. Crystallographic data are summarized below (for
published data, only CCDC deposit numbers are given).15 Thermal
ellipsoid models and details of refinements for the crystals are
described in supplementary data.
(300 MHz CDC13)
d 7.28 (1H, t, J 7.9 Hz), 5.73 (2H, d, J 7.9 Hz), 4.26
(2H, s), 2.84 (6H, d, J 5.1 Hz); 13C NMR (75 MHz, CDC13)
d 159.1,
139.0, 93.9, 29.1; m/z (EI) 137; HRMS (EI): Mþ, found 137.0945.
C7H11N3 requires 137.0953.
4.1.16. 1,3-Bis(formamido)benzene. A mixture of formic acid (80 mL,
2.1 mol) and acetic anhydride (170 mL, 1.8 mol) was heated at 70 ꢁC
for 2 h, then cooled to ꢀ10 ꢁC. A solution of m-phenylenediamine
(25 g, 0.23 mol) in THF (150 mL) was added dropwise to the above
solution over a period of 4 h at ꢀ10 ꢁC with stirring. After a further
15 min, the product was collected by filtration (17.9 g, 47%). Col-
orless powder. Mp 156.5e159.0 ꢁC; [Anal. Found: C, 58.36; H, 4.77;
N, 17.11. C8H8N2O2 requires C, 58.53; H, 4.91; N, 17.06%]; 1H NMR
Compound 1: CCDC-625148.
Compound 2: C13H12N2O, Mr¼212.25, Monoclinic, P21/c,
¼107.8690(10)ꢁ,
ꢀ
a¼11.5293(12), b¼7.5151(8), c¼13.2121(14) A,
b
3
V¼1089.5(2) A , Z¼4, Dc¼1.294 Mg mꢀ3, 2qmax¼54.36ꢁ, T¼120 K,
ꢀ
5171 reflections measured, 2149 unique (Rint¼0.0202),
m
(Mo K
a)¼
0.084 mmꢀ1. The final R1 and wR2 were 0.0497 and 0.1148 (all data).
CCDC-836681.
(300 MHz, DMSO-d6, 150 ꢁC)
7.21 (3H, m); m/z (EI) 164.
d 9.59 (2H, s), 8.38 (2H, s), 7.59 (1H, s),
Compound 3: C13H12N2O, Mr¼212.25, Tetragonal, I41/a,
3
ꢀ
ꢀ
a¼b¼23.9263(8), c¼7.8199(5) A, V¼4476.6(4) A , Z¼16,
4.1.17. N,N0-Dimethyl-1,3-diaminobenzene (16). To a solution of 16
(1.5 g, 9.15 mmol) in THF, borane dimethyl sulfide complex
(4.34 mL, 45.8 mmol) was added at 0 ꢁC, followed by stirring at the
same temperature for 0.5 h, then for 1.5 h at ambient temperature.
Dc¼1.260 Mg mꢀ3, 2qmax¼54.30ꢁ, T¼150 K, 10,543 reflections
measured, 2328 unique (Rint¼0.0240),
m
(Mo K
a
)¼0.082 mmꢀ1. The
final R1 and wR2 were 0.0483 and 0.0933 (all data). CCDC-836683.
Compound 4: CCDC-625151.

I. Okamoto et al. / Tetrahedron 67 (2011) 8536e8543
8543
Compound 5: CCDC-625149.
associated with this article can be found, in the online version, at
doi:10.1016/j.tet.2011.08.085.
Compound 6: C20H18N4O2, Mr¼346.38, Monoclinic, P21/n,
¼106.8140(10)ꢁ,
ꢀ
a¼11.2733(7), b¼11.8136(7), c¼13.1965(8) A,
b
3
V¼1682.35(18) A , Z¼4, Dc¼1.368 Mg mꢀ3, 2qmax¼56.42ꢁ, T¼150 K,
ꢀ
References and notes
9207 reflections measured, 3791 unique (Rint¼0.0152),
m
(Mo K
a
)¼
0.091 mmꢀ1. The final R1 and wR2 were 0.0447 and 0.1009 (all data).
CCDC-836685.
1. The Amide Linkage; Greenberg, A., Breneman, C. M., Liebman, J. F., Eds.; Wiley:
New York, NY, 2003.
Compound 7: C20H18N4O2$H2O, Mr¼364.40, Orthorhombic
2. cisetrans Isomerization in Biochemistry; Greenberg, A., Breneman, C. M., Dugave,
C., Eds.; Wiley-VCH: Weinheim, 2006.
ꢀ
Pnma, a¼7.0821(4), b¼21.7993(14), c¼11.6085(7) A, V¼1792.18(19)
3. (a) Itai, A.; Toriumi, Y.; Tomioka, N.; Kagechika, H.; Azumaya, I.; Shudo, K.
Tetrahedron Lett. 1989, 30, 6177e6180; (b) Azumaya, I.; Kagechika, H.; Fujiwara,
Y.; Itoh, M.; Yamaguchi, K.; Shudo, K. J. Am. Chem. Soc. 1991, 113, 2833e2838.
4. (a) Azumaya, I.; Yamaguchi, K.; Okamoto, I.; Kagechika, H.; Shudo, K. J. Am.
Chem. Soc. 1995, 117, 9083e9084; (b) Azumaya, I.; Okamoto, I.; Nakayama, S.;
Tanatani, A.; Yamaguchi, K.; Shudo, K.; Kagechika, H. Tetrahedron 1999, 55,
11237e11246.
A , Z¼4, Dc¼1.351 Mg mꢀ3, 2qmax¼56.52ꢁ, T¼150 K, 9312 reflections
3
ꢀ
measured, 2136 unique (Rint¼0.0180),
m
(Mo K
a
)¼0.093 mmꢀ1. The
final R1 and wR2 were 0.0409 and 0.1036 (all data). CCDC-836687.
Perchlorate 1H: C12H13N3O$2ClO4, Mr¼414.15, Monoclinic, Cc,
a¼14.664(6),
b¼8.180(3),
c¼13.523(5)
A,
b
¼95.160(5)ꢁ,
ꢀ
V¼1615.6(11) A , Z¼4, Dc¼1.703 Mg mꢀ3, 2qmax¼56.16ꢁ, T¼150 K,
3
ꢀ
5. Azumaya, I.; Kagechika, H.; Yamaguchi, K.; Shudo, K. Tetrahedron Lett. 1996, 37,
5003e5006.
4286 reflections measured, 2434 unique (Rint¼0.0306),
m
(Mo K
a
)¼
6. (a) Tanatani, A.; Yokoyama, A.; Azumaya, I.; Takakura, Y.; Mitsui, C.; Shiro, M.;
Uchiyama, M.; Muranaka, A.; Kobayashi, N.; Yokozawa, T. J. Am. Chem. Soc. 2005,
127, 8553e8561; (b) Chabaud, L.; Clayden, J.; Helliwell, M.; Page, A.; Raftery, J.;
0.459 mmꢀ1. The final R1 and wR2 were 0.0719 and 0.1675 (all data).
CCDC-836680.
ꢁ
Vallverdu, L. Tetrahedron 2010, 66, 6936e6957; (c) Yue, N. L. S.; Jennings, M. C.;
Perchlorate 2H: C13H13N2O$ClO4, Mr¼312.70, Monoclinic, P21/c,
Puddephatt, R. J. Inorg. Chem. 2005, 44, 1125e1131; (d) Masu, H.; Sakai, M.;
Kishikawa, K.; Yamamoto, M.; Yamaguchi, K.; Kohmoto, S. J. Org. Chem. 2005,
70, 1423e1431; (e) Nishimura, T.; Maeda, K.; Yashima, E. Chirality 2004, 16,
S12eS22.
a¼6.3357(5), b¼7.4244(6), c¼28.397(2) A,
b
¼95.4480(10)ꢁ,
ꢀ
V¼1329.71(18) A , Z¼4, Dc¼1.562 Mg mꢀ3, 2qmax¼54.40ꢁ, T¼120 K,
3
ꢀ
6404 reflections measured, 2638 unique (Rint¼0.0222),
m
(Mo K
a
)¼
7. (a) Balzani, V.; Credi, A.; Venturi, M. Molecular Devices and Machines; Wiley-
VCH: Weinheim, 2004; (b) Feringa, B. L. In Molecular Switches; Wiley-VCH:
Weinheim, 2001; (c) Irie, M. Chem. Rev. 2000, 100, 1685e1716.
8. (a) Kagechika, H.; Himi, T.; Kawachi, E.; Shudo, K. J. Med. Chem. 1989, 32,
2292e2296; (b) Kagechika, H. Curr. Med. Chem. 2002, 9, 591e608.
0.312 mmꢀ1. The final R1 and wR2 were 0.0429 and 0.0883 (all data).
CCDC-836682.
Perchlorate 3H: C13H13N2O$ClO4, Mr¼312.70, Triclinic, Pꢀ1,
ꢀ
a¼6.4095(10), b¼9.0554(14), c¼12.1921(19) A,
a
¼88.436(2),
ꢁ
9. (a) Clayden, J.; Lund, A.; Vallverdu, L.; Helliwell, M. Nature 2004, 431, 966e971;
3
ꢀ
ꢀ3
ꢁ
b
¼79.761(2),
g
¼76.214(2) , V¼676.22(18) A , Z¼2, Dc¼1.536 Mg m
,
(b) Kern, D.; Zuiderweg, E. R. P. Curr. Opin. Struct. Biol. 2003, 13, 748e757; (c)
Feringa, B. L. Acc. Chem. Res. 2001, 34, 504e513; (d) Balzani, V.; Credi, A.;
Raymo, F. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2000, 39, 3348e3391.
10. Okamoto, I.; Yamasaki, R.; Sawamura, M.; Kato, T.; Nagayama, N.; Takeya, T.;
Tamura, O.; Masu, H.; Azumaya, I.; Yamaguchi, K.; Kagechika, H.; Tanatani, A.
Org. Lett. 2007, 9, 5545e5547.
11. (a) Okamoto, I.; Nabeta, M.; Yamamoto, M.; Mikami, M.; Takeya, T.; Tamura, O.
Tetrahedron Lett. 2006, 47, 7143e7146; (b) Yamasaki, R.; Tanatani, A.; Azumaya,
I.; Masu, H.; Yamaguchi, K.; Kagechika, H. Cryst. Growth Des. 2006, 6,
2007e2010.
12. (a) Burchell, T. J.; Eisler, D. J.; Puddephatt, R. J. Cryst. Growth Des. 2006, 6,
974e982; (b) Recker, J.; Tomcik, D. J.; Parquette, J. R. J. Am. Chem. Soc. 2000, 122,
10298e10307; (c) Goto, H.; Heemstra, J. M.; Hill, D. J.; Moore, J. S. Org. Lett.
2004, 6, 889e892; (d) Berl, V.; Huc, I.; Khoury, R. G.; Krische, M. J.; Lehn, J.-M.
Nature 2000, 407, 720e723; (e) Fujita, M.; Oguro, D.; Miyazawa, M.; Oka, H.;
Yamaguchi, K.; Ogura, K. Nature 1995, 378, 469e471.
13. (a) Dolain, C.; Maurizot, V.; Huc, I. Angew. Chem., Int. Ed. 2003, 42, 2738e2740;
(b) Abe, H.; Masuda, N.; Waki, M.; Inouye, M. J. Am. Chem. Soc. 2005, 127,
16189e16196; (c) Ikeda, A.; Tsudera, T.; Shinkai, S. J. Org. Chem. 1997, 62,
3568e3574.
2
qmax¼53.72ꢁ, T¼150 K, 3223 reflections measured, 2490 unique
(Rint¼0.0121),
m
(Mo K
a
)¼0.307 mmꢀ1. The final R1 and wR2 were
0.0550 and 0.1316 (all data). CCDC-836684.
Perchlorate 4H: CCDC-625152.
Perchlorate 5H: CCDC-625150.
Perchlorate 6H: C20H20N4O2$2ClO4, Mr¼547.30, Monoclinic, P21/
n, a¼16.470(4), b¼16.248(4), c¼16.467(4) A,
b
¼93.553(3)ꢁ,
ꢀ
V¼4398.3(18) A , Z¼8, Dc¼1.653 Mg mꢀ3, 2qmax¼55.24ꢁ, T¼120 K,
3
ꢀ
24086 reflections measured, 9747 unique (Rint¼0.0526),
m (Mo
Ka
)¼0.364 mmꢀ1. The final R1 and wR2 were 0.0988 and 0.1450 (all
data). CCDC-836686.
Perchlorate 7H: C20H20N4O2$2ClO4, Mr¼547.30, Orthorhombic
3
ꢀ
ꢀ
Fdd2, a¼12.7608(11), b¼28.645(4), c¼12.4297(12) A, V¼4543.5(9)A ,
Z¼8, Dc¼1.600 Mg mꢀ3, 2qmax¼135.94ꢁ, T¼150 K, 2058 reflections
measured, 1412 unique (Rint¼0.0222),
m
(Cu K
a
)¼3.173 mmꢀ1. The
14. Okamoto, I.; Nabeta, M.; Hayakawa, Y.; Morita, N.; Takeya, T.; Masu, H.; Azu-
final R1 and wR2 were 0.0418 and 0.0934 (all data). CCDC-836688.
maya, I.; Tamura, O. J. Am. Chem. Soc. 2007, 129, 1892e1893.
15. Okamoto, I.; Nabeta, M.; Minami, T.; Nakashima, A.; Morita, N.; Takeya, T.;
Masu, H.; Azumaya, I.; Tamura, O. Tetrahedron Lett. 2007, 48, 573e577.
16. Singha, N. C.; Sathyanarayana, D. N. J. Mol. Struct. 1997, 403, 123e135.
17. (a) Perlepes, S. P.; Kabanos, T.; Hondrellis, V.; Tsangaris, J. M. Inorg. Chim. Acta
1988, 150, 13e23; (b) Bould, J.; Brisdon, B. J. Inorg. Chim. Acta 1976, 19, 159e163;
(c) Nonoyama, M.; Tomita, S.; Yamasaki, K. Inorg. Chim. Acta 1975, 12, 33e37.
18. (a) Zhu, J.; Parra, R. D.; Zeng, H.; Skrzypczak-Jankun, E.; Zeng, X. C.; Gong, B. J.
Am. Chem. Soc. 2000, 122, 4219e4220; (b) Hofacker, A. L.; Parquette, J. R. Angew.
Chem., Int. Ed. 2005, 44, 1053e1057; (c) Hamuro, Y.; Geib, S. J.; Hamilton, A. D. J.
Am. Chem. Soc. 1997, 119, 10587e10593; (d) Kawamoto, T.; Hammes, B. S.;
Haggerty, B.; Yap, G. P. A.; Rheingold, A. L.; Borovik, A. S. J. Am.Chem. Soc. 1996,
118, 285e286.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Japan Society for the Promotion of Science.
Supplementary data
Supplementary data are available in PDF format: X-ray crystal-
lographic data for 2,3,6,7,1H,2H,3H,6H and 7H. Supplementary data
19. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112e122.